BRIP1c.143C>AUncertain significance

Print report

Variant interpretation report

BRIP1 c.143C>A, p.(Thr48Lys)

NM_032043.3:c.143C>A NP_114432.2:p.(Thr48Lys) View identifiers

Classification

Uncertain significance

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.

Uncertain.The recorded classification is uncertain significance.

In plain language

Gene-level background from the recorded interpretation.

About BRIP1

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 supporting (benign) · 2 supporting (pathogenic)
Expert rules: Not recorded
Other laboratories (ClinVar): 5 Uncertain significance
Pipeline record: 20 Jul 2026 · version 7.0.4

Evidence considered

View criteria

Applied evidence criteria

PM2 (supporting): NM_032043.3:c.143C>A is extremely rare in population databases: gnomAD v2.1 allele frequency is 0.00319% (1/31,388 alleles, genomes only, 0 homozygotes) and gnomAD v4.1 allele frequency is 0.00037% (6/1,613,830 alleles, 0 homozygotes) with grpmax filtering allele frequency of 1.24×10⁻⁶. Both are well below the 0.1% threshold for PM2 at supporting strength.
PP3 (supporting): In silico analysis supports a deleterious effect of NM_032043.3:c.143C>A (p.Thr48Lys). REVEL score is 0.728, above the 0.7 threshold for damaging prediction. Multiple clinical laboratories (GeneDx, Ambry Genetics, LabCorp) also cite in silico evidence for a deleterious effect in their ClinVar submissions. BayesDel score is 0.307, which is borderline; however, the weight of evidence from REVEL and the non-conservative nature of the Thr→Lys substitution supports a deleterious prediction at the supporting level.
BP1 (supporting): BRIP1 is a moderate-penetrance breast and ovarian cancer predisposition gene in which the predominant disease-causing mechanism is protein truncation. As established by Stratton and Rahman (2008, PMID:18163131), most disease-causing mutations in BRIP1 result in premature protein truncation or nonsense-mediated RNA decay, with only a small proportion likely to be rare missense variants disrupting critical functions. NM_032043.3:c.143C>A is a missense variant (p.Thr48Lys), and therefore BP1 applies at supporting benign strength.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 2 Benign evidence criteria: 1

Pathogenic criteria applied · 2

PM2Supporting

PM2 · supporting

NM_032043.3:c.143C>A is extremely rare in population databases: gnomAD v2.1 allele frequency is 0.00319% (1/31,388 alleles, genomes only, 0 homozygotes) and gnomAD v4.1 allele frequency is 0.00037% (6/1,613,830 alleles, 0 homozygotes) with grpmax filtering allele frequency of 1.24×10⁻⁶. Both are well below the 0.1% threshold for PM2 at supporting strength.

PP3Supporting

PP3 · supporting

In silico analysis supports a deleterious effect of NM_032043.3:c.143C>A (p.Thr48Lys). REVEL score is 0.728, above the 0.7 threshold for damaging prediction. Multiple clinical laboratories (GeneDx, Ambry Genetics, LabCorp) also cite in silico evidence for a deleterious effect in their ClinVar submissions. BayesDel score is 0.307, which is borderline; however, the weight of evidence from REVEL and the non-conservative nature of the Thr→Lys substitution supports a deleterious prediction at the supporting level.

Benign criteria applied · 1

BP1Supporting

BP1 · supporting

BRIP1 is a moderate-penetrance breast and ovarian cancer predisposition gene in which the predominant disease-causing mechanism is protein truncation. As established by Stratton and Rahman (2008, PMID:18163131), most disease-causing mutations in BRIP1 result in premature protein truncation or nonsense-mediated RNA decay, with only a small proportion likely to be rare missense variants disrupting critical functions. NM_032043.3:c.143C>A is a missense variant (p.Thr48Lys), and therefore BP1 applies at supporting benign strength.

Recorded classification: Uncertain significance

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, PP3 supporting, BP1 supporting benign; combination = 2 supporting + 1 supporting benign, which maps to VUS.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

6 / 1,613,830 alleles

gnomAD v4.1: 6 / 1,613,830 alleles. Recorded AF 3.71786e-06. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 3.18593e-05; MAF= 0.00319%, 1/31388 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.48593e-05; MAF= 0.00649%, 1/15418 alleles, homozygotes = 0).

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · PP3 → SpliceAI ↗

ClinVar submissions

5 reported laboratory submissions

5 Uncertain significance. ClinVar API review status: criteria provided, multiple submitters, no conflicts.

Context only ClinVar ↗

Functional evidence

Statement recorded

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRIP1, a DEAH helicase, is altered by mutation and amplification in various cancers, including breast cancer and melanoma.

No listed criterion applied OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

No matching record reported

This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

29 criteria with recorded statuses: 3 met · 21 not met · 1 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_032043.3:c.143C>A (p.Thr48Lys) is a missense variant in BRIP1, a moderate-penetrance breast and ovarian cancer predisposition gene where the predominant disease mechanism is protein truncation.

This variant is extremely rare in population databases: gnomAD v2.1 allele frequency is 0.00319% (1/31,388 alleles) and v4.1 allele frequency is 0.00037% (6/1,613,830 alleles) with no homozygotes observed, meeting PM2 at supporting strength.

In silico analysis supports a deleterious effect: REVEL score of 0.728 exceeds the 0.7 threshold for damaging prediction; the Thr48Lys substitution is non-conservative, replacing a polar uncharged residue with a positively charged one, meeting PP3 at supporting strength.

BRIP1 disease-causing mutations predominantly result in protein truncation or nonsense-mediated RNA decay. This missense variant is not consistent with the primary disease mechanism, meeting BP1 at supporting benign strength.

This variant has been reported in ClinVar as Uncertain significance by 5 clinical laboratories (Variation ID 234642, 1-star review status). No functional studies, segregation data, de novo observations, or case-control data are available.

No functional studies or literature directly testing NM_032043.3:c.143C>A (p.Thr48Lys) or a systematically characterized residue range including position 48 were identified. The variant has not been reported in COSMIC and OncoKB reports Unknown Oncogenic Effect.

The evidence profile includes one pathogenic supporting criterion (PM2), one pathogenic supporting criterion (PP3), and one benign supporting criterion (BP1), resulting in net neutral evidence. Based on generic ACMG/AMP 2015 combination rules, this variant is classified as a Variant of Uncertain Significance.

Met · 3

PM2 SupportingNM_032043.3:c.143C>A is extremely rare in population databases: gnomAD v2.1 allele frequency is 0.00319% (1/31,388 alleles, genomes only, 0 homozygotes) and gnomAD v4.1 allele frequency is 0.00037% (6/1,613,830 alleles, 0 homozygotes) with grpmax filtering allele frequency of 1.24×10⁻⁶. Both are well below the 0.1% threshold for PM2 at supporting strength. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF = 0.00319% (1/31
388 alleles)
gnomAD v4.1 AF = 0.00037% (6/1
613
830 alleles)
grpmax FAF = 1.24e-06
0 homozygotes in both datasets
Both AFs well below the 0.1% PM2 threshold

Sources

gnomad_v2 ↗gnomad_v4 ↗

PP3 SupportingIn silico analysis supports a deleterious effect of NM_032043.3:c.143C>A (p.Thr48Lys). REVEL score is 0.728, above the 0.7 threshold for damaging prediction. Multiple clinical laboratories (GeneDx, Ambry Genetics, LabCorp) also cite in silico evidence for a deleterious effect in their ClinVar submissions. BayesDel score is 0.307, which is borderline; however, the weight of evidence from REVEL and the non-conservative nature of the Thr→Lys substitution supports a deleterious prediction at the supporting level. Details ▾Hide ▴

Evidence considered

REVEL score = 0.728 (>0.7 damaging threshold)
BayesDel score = 0.306828 (borderline)
Thr→Lys is a non-conservative amino acid substitution (polar uncharged→positively charged)
SpliceAI max delta = 0.00 (no splice impact)
Three clinical laboratories cite in silico evidence for pathogenicity in ClinVar

Sources

revelbayesdelclinvar ↗

BP1 SupportingBRIP1 is a moderate-penetrance breast and ovarian cancer predisposition gene in which the predominant disease-causing mechanism is protein truncation. As established by Stratton and Rahman (2008, PMID:18163131), most disease-causing mutations in BRIP1 result in premature protein truncation or nonsense-mediated RNA decay, with only a small proportion likely to be rare missense variants disrupting critical functions. NM_032043.3:c.143C>A is a missense variant (p.Thr48Lys), and therefore BP1 applies at supporting benign strength. Details ▾Hide ▴

Evidence considered

Stratton & Rahman (2008): 'most of the disease-causing mutations result in premature protein truncation or nonsense-mediated RNA decay' in BRIP1
Missense variants are not the primary disease mechanism in BRIP1
Position 48 (p.Thr48Lys) is in the N-terminal region outside the helicase domain

Sources

PMID:18163131 ↗

Not met · 21 · evaluated, threshold not reached

PVS1 NM_032043.3:c.143C>A is a missense variant (p.Thr48Lys) in BRIP1 exon 3. It does not fall into any default PVS1 null-variant category (nonsense, frameshift, or canonical ±1,2 splice consensus). The generic PVS1 decision tree per ClinGen SVI recommendations (PMC6185798) does not apply to missense variants. Details ▾Hide ▴

Evidence considered

Variant is missense (c.143C>A
p.Thr48Lys)
not a null variant
Confirmed as 'other' bucket in PVS1 variant assessment
generic PVS1 framework not applicable

Sources

pvs1_variant_assessmentpvs1_generic_framework ↗

PS1 No evidence of a different nucleotide change at codon 48 (same amino acid change p.Thr48Lys) that has been reported as pathogenic in the literature or databases. Details ▾Hide ▴

Evidence considered

No alternate nucleotide change at codon 48 producing p.Thr48Lys identified

PS2 No de novo occurrence data (with confirmed maternity and paternity) available for NM_032043.3:c.143C>A. Details ▾Hide ▴

Evidence considered

No de novo data identified in ClinVar submissions or literature

PS3 No functional studies were identified that directly tested NM_032043.3:c.143C>A (p.Thr48Lys) or a systematically characterized residue range that includes position 48. OncoKB reports Unknown Oncogenic Effect with no variant-specific functional evidence. The full-text literature review did not identify any experimental functional data for this variant. Details ▾Hide ▴

Evidence considered

No variant-specific functional studies found in literature or OncoKB
No systematic range characterization including residue 48 identified

Still missing

No functional data available for this variant

Sources

oncokb ↗

PS4 No case-control studies or cohort data establishing statistically significant enrichment of NM_032043.3:c.143C>A in affected individuals versus controls are available. The variant is reported in ClinVar as Uncertain significance by 5 clinical laboratories without prevalence data. Details ▾Hide ▴

Evidence considered

Variant is classified as VUS in ClinVar by 5 submitters
No case-control or odds-ratio data available

Still missing

No case-control data for this variant

Sources

clinvar ↗

PM1 Position 48 is located in the N-terminal region of BRIP1, outside the helicase domain (approximately residues 250–600). Cancerhotspots.org does not identify this residue as statistically significant. No literature evidence supports residue 48 as lying within a critical functional domain. Details ▾Hide ▴

Evidence considered

Residue 48 is N-terminal
outside the DEAH helicase domain (aa ~250–600)
Not a statistically significant hotspot per cancerhotspots.org

Still missing

No domain-level characterization of the N-terminal region of BRIP1 for PM1

PM5 No same-residue pathogenic comparator variant was identified at codon 48. The PM5 candidate harvest did not find any alternate amino acid change at position 48 classified as pathogenic or likely pathogenic in ClinVar. Details ▾Hide ▴

Evidence considered

PM5 candidate search returned 0 same-residue candidates

Sources

pm5_candidates

PM6 No de novo occurrence of NM_032043.3:c.143C>A has been reported. PM6 requires observation of the variant as de novo with unconfirmed maternity/paternity. Details ▾Hide ▴

Evidence considered

No de novo data available

PP1 No family segregation data are available for NM_032043.3:c.143C>A. PP1 requires cosegregation of the variant with disease in multiple affected family members. Details ▾Hide ▴

Evidence considered

No segregation data available

Still missing

No family studies available

PP4 No patient phenotype data or family history information is available for the individual(s) carrying NM_032043.3:c.143C>A. PP4 requires a phenotype or family history highly specific for BRIP1-related disease. Details ▾Hide ▴

Evidence considered

No proband phenotype data available

Still missing

No patient phenotype available

PP5 No reputable source reports NM_032043.3:c.143C>A as pathogenic. ClinVar classification is Uncertain significance with review status 'criteria provided, single submitter' (1-star). The ClinGen PP5/BP6 rule requires 3-star expert panel review to apply PP5 at supporting strength, which is not met here. No other reputable source classifies this variant as pathogenic. Details ▾Hide ▴

Evidence considered

ClinVar classification: Uncertain significance (Variation ID 234642)
Review status: criteria provided
single submitter (1-star)
No expert panel (3-star) classification available
5 clinical laboratories all report VUS

Sources

clinvar ↗

BA1 NM_032043.3:c.143C>A allele frequency is 0.00319% in gnomAD v2.1 and 0.00037% in gnomAD v4.1, both far below the 1% BA1 threshold. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF = 0.00319% (<< 1%)
gnomAD v4.1 AF = 0.00037% (<< 1%)

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 NM_032043.3:c.143C>A allele frequency is 0.00319% in gnomAD v2.1 and 0.00037% in gnomAD v4.1, both far below the 0.3% BS1 threshold. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF = 0.00319% (<< 0.3%)
gnomAD v4.1 AF = 0.00037% (<< 0.3%)

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 NM_032043.3:c.143C>A has not been observed in the homozygous state in gnomAD (0 homozygotes across v2.1 and v4.1 combined) and has not been reported in trans with a known pathogenic BRIP1 variant. Details ▾Hide ▴

Evidence considered

0 homozygotes in gnomAD v2.1 and v4.1
No evidence of occurrence in trans with a pathogenic variant

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS3 No well-established functional studies demonstrate that NM_032043.3:c.143C>A (p.Thr48Lys) has no deleterious effect on protein function or splicing. Details ▾Hide ▴

Evidence considered

No functional studies showing benign effect identified

Still missing

No functional data available

BS4 No nonsegregation data are available for NM_032043.3:c.143C>A. BS4 requires lack of segregation with disease in affected family members. Details ▾Hide ▴

Evidence considered

No segregation data available

Still missing

No family studies available

BP2 NM_032043.3:c.143C>A has not been observed in trans with a known pathogenic BRIP1 variant. BRIP1-related cancer predisposition is autosomal dominant; observation in trans with a pathogenic variant would be required for BP2. Details ▾Hide ▴

Evidence considered

No observation in trans with a pathogenic variant

BP4 In silico analysis does not support a benign impact. REVEL score of 0.728 (>0.7 threshold) predicts a damaging effect on protein structure/function, contradicting BP4. SpliceAI shows no splice impact (max delta = 0.00), but the REVEL score indicates a deleterious missense change. Details ▾Hide ▴

Evidence considered

REVEL = 0.728 predicts damaging
BayesDel = 0.307 (borderline)
SpliceAI max delta = 0.00
Multiple predictors do not support benign
REVEL contradicts BP4

Sources

revelbayesdelspliceai ↗

BP5 No alternate molecular basis for disease has been identified in an individual carrying NM_032043.3:c.143C>A. BP5 requires an alternative cause of the phenotype to be established. Details ▾Hide ▴

Evidence considered

No alternate molecular diagnosis reported

BP6 No reputable source reports NM_032043.3:c.143C>A as benign. ClinVar classification is Uncertain significance with review status 'criteria provided, single submitter' (1-star). BP6 requires a reputable source to classify the variant as benign, which is not met. Details ▾Hide ▴

Evidence considered

ClinVar: Uncertain significance
not benign
1-star review status

Sources

clinvar ↗

PS5 No pathogenic variant at codon 48 has been reported through non-ClinVar (literature-based) sources. PS5 requires a different pathogenic variant at the same codon from a reputable non-ClinVar source. Details ▾Hide ▴

Evidence considered

No literature report of a different pathogenic variant at codon 48

Not assessed · 1 · no assessment recorded

PP2 Insufficient data to assess whether BRIP1 has a low rate of benign missense variation. No missense constraint metric (e.g., Z-score, o/e ratio) is available in the evidence packet for this gene. Details ▾Hide ▴

Evidence considered

No missense constraint data available for BRIP1 in evidence packet

Still missing

Missense constraint metrics (Z-score
o/e) not available for BRIP1

Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴

PM3 N/APM3 applies to recessive disorders where the variant is observed in trans with a pathogenic variant. BRIP1-related cancer predisposition is autosomal dominant; this criterion is not applicable. Details ▾Hide ▴

No further detail was recorded.

PM4 N/ANM_032043.3:c.143C>A is a missense substitution (p.Thr48Lys), not a protein length-altering variant (stop-loss, in-frame indel, or initiation codon change). PM4 does not apply. Details ▾Hide ▴

No further detail was recorded.

BP3 N/ANM_032043.3:c.143C>A is a substitution variant, not an in-frame insertion/deletion. BP3 applies only to in-frame indels in repetitive regions without a known function. Details ▾Hide ▴

No further detail was recorded.

BP7 N/ANM_032043.3:c.143C>A is a missense variant (p.Thr48Lys), not a synonymous or non-coding variant. BP7 applies only to synonymous variants without splice impact. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: BRIP1
Transcript: NM_032043.3
Coding (HGVS c.): NM_032043.3:c.143C>A
Protein (HGVS p.): NP_114432.2:p.(Thr48Lys)
GRCh38: chr17:61859858 G>T
GRCh37: chr17:59937219 G>T
ClinVar: 234642

Gene diagram

Every interpreted variant in BRIP1, mapped onto the exon structure of NM_032043.3. Select a row to find it on the plot.

BRIP1NM_032043.3

Fetching transcript structure from UCSC…

Exons

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Transcript span

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Strand

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Variants mapped

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Source

UCSC ncbiRefSeqCurated

All variants in BRIP1 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 6 / 1,613,830 alleles AF 3.72e-06 · 0 homozygotes · FAF 1.24e-06

gnomAD v2.1 1 / 31,388 alleles AF 3.19e-05 · 0 homozygotes

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 3.7e-06 · 6 / 1,613,830 alleles · 0 hom · FAF 1.2e-06

European (Finnish)1 / 64,010	1.6e-05
European (non-Finnish)5 / 1,179,898	4.2e-06

0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.

gnomAD v2.1

AF 3.2e-05 · 1 / 31,388 alleles · 0 hom

European (non-Finnish)1 / 15,418

6.5e-05

0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 3.71786e-06; MAF= 0.00037%, 6/1613830 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 1.56226e-05; MAF= 0.00156%, 1/64010 alleles, homozygotes = 0); grpmax FAF= 1.24e-06.

gnomAD v2.1

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown

-0.000

Pangolin splice gain

0.010

Other predictors

REVEL: 0.728
BayesDel: 0.307

How the predictions were used

Evidence considered

REVEL score = 0.728 (>0.7 damaging threshold)
BayesDel score = 0.306828 (borderline)
Thr→Lys is a non-conservative amino acid substitution (polar uncharged→positively charged)
SpliceAI max delta = 0.00 (no splice impact)
Three clinical laboratories cite in silico evidence for pathogenicity in ClinVar

Sources

revelbayesdelclinvar ↗

Evidence considered

REVEL = 0.728 predicts damaging
BayesDel = 0.307 (borderline)
SpliceAI max delta = 0.00
Multiple predictors do not support benign
REVEL contradicts BP4

Sources

revelbayesdelspliceai ↗

BP7 N/ANM_032043.3:c.143C>A is a missense variant (p.Thr48Lys), not a synonymous or non-coding variant. BP7 applies only to synonymous variants without splice impact. Details ▾Hide ▴

No further detail was recorded.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.728. BayesDel score = 0.306828.

7 paper records listed. 1 cited in the classification. None of the listed paper records explicitly indicates that the variant is named.

Cited in the classification

The emerging landscape of breast cancer susceptibility.

Stratton MR et al. · 2008 Jan

Review by Stratton and Rahman describing the genetic architecture of breast cancer susceptibility, including BRIP1 as a rare moderate-penetrance gene. States that in BRIP1, 'most of the disease-causing mutations result in premature protein truncation or nonsense-mediated RNA decay.' NM_032043.3:c.143C>A is not discussed.
→ BP1 Does not name this variant
PMID 18163131 ↗
Source detail

In CHEK2, ATM, BRIP1 and PALB2, most of the disease-causing mutations result in premature protein truncation or nonsense-mediated RNA decay through nonsense codons or translational frameshifts.

Location Page 18, column 2, paragraph 1

Other recorded publications

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Standards and guidelines for the interpretation of sequence variants (ACMG/AMP 2015). Provides the generic classification framework and evidence combination rules used for this assessment. NM_032043.3:c.143C>A is not discussed.
Does not name this variant
PMID 25741868 ↗
Whole-exome sequencing of ovarian cancer families uncovers putative predisposition genes.

Zhu Q et al. · 2020

Whole-exome sequencing study of 158 patients from 140 ovarian cancer families to identify new predisposition genes. BRIP1 is discussed as a known OC predisposition gene but NM_032043.3:c.143C>A is not mentioned in the full text.
Does not name this variant
PMID 31265121 ↗
Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.

Moyer VA et al. · 2014

USPSTF 2014 recommendation statement on BRCA-related cancer risk assessment, genetic counseling, and genetic testing. Focuses exclusively on BRCA1/BRCA2; BRIP1 and NM_032043.3:c.143C>A are not discussed.
Does not name this variant
PMID 24366376 ↗
Summaries for patients. Assessing the genetic risk for BRCA-related breast or ovarian cancer in women: recommendations from the U.S. Preventive Services Task Force.

2014

Patient-facing summary of the USPSTF 2014 BRCA-related cancer screening recommendations. Does not discuss BRIP1 or NM_032043.3:c.143C>A.
Does not name this variant
PMID 24366402 ↗
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement.

USPSTF 2019 updated recommendation statement on BRCA-related cancer risk assessment, genetic counseling, and genetic testing. Focuses exclusively on BRCA1/BRCA2; BRIP1 and NM_032043.3:c.143C>A are not discussed.
Does not name this variant
PMID 31429903 ↗
ACMG SF v3.1 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG).

ACMG SF v3.1 policy statement on secondary findings in clinical exome and genome sequencing. Lists genes recommended for return of secondary findings. NM_032043.3:c.143C>A is not discussed.
Does not name this variant
PMID 35802134 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 6 / 1,613,830 recorded alleles Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗

ClinVar 5 Uncertain significance Open source ↗

COSMIC Captured COSMIC source record Open source ↗

Cancer hotspots Captured Cancer Hotspots source record Open source ↗

OncoKB Captured OncoKB source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

gnomAD v2.1

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Uncertain significance (5 clinical laboratories). (ClinVarID = 234642)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.728. BayesDel score = 0.306828.

Functional

Somatic

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.