BRIP1c.2085G>ALikely benign

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Variant interpretation report

BRIP1 c.2085G>A, p.(Leu695=)

NM_032043.3:c.2085G>A NP_114432.2:p.(Leu695=) View identifiers

Classification

Likely benign

Variant description:

No variant summary was recorded for this case.

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

Likely benign.A likely benign classification under the recorded framework.

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: 3 supporting (benign)
Expert rules: Not recorded
Other laboratories (ClinVar): 3 Likely benign
Pipeline record: 26 Jun 2026 · version 7.0.0

Evidence considered

View criteria

Applied evidence criteria

BP4 (supporting): SpliceAI predicts no splicing impact for this synonymous variant (max delta score 0.00 across all acceptor and donor positions). REVEL and BayesDel do not provide scores for synonymous variants. The available computational evidence, while limited to splicing prediction, supports a benign interpretation.
BP6 (supporting): ClinVar reports NM_032043.3:c.2085G>A as Likely benign (VariationID 530367), based on submissions from three clinical diagnostic laboratories (Color Health, Invitae/Labcorp, Ambry Genetics). Multiple reputable clinical laboratories have independently classified this variant as likely benign, meeting BP6 criteria for a reputable source reporting the variant as benign.
BP7 (supporting): NM_032043.3:c.2085G>A is a synonymous variant at codon 695 (p.Leu695=) in exon 14 of BRIP1. SpliceAI predicts no impact on splicing (all delta scores = 0.00; donor/acceptor gain/loss scores all at zero). The variant is not located in a highly conserved splice region. BP7 is met for a synonymous variant with no predicted effect on splicing.

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: 0 Benign evidence criteria: 3

Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 3

BP4Supporting

BP4 · supporting

SpliceAI predicts no splicing impact for this synonymous variant (max delta score 0.00 across all acceptor and donor positions). REVEL and BayesDel do not provide scores for synonymous variants. The available computational evidence, while limited to splicing prediction, supports a benign interpretation.

BP6Supporting

BP6 · supporting

ClinVar reports NM_032043.3:c.2085G>A as Likely benign (VariationID 530367), based on submissions from three clinical diagnostic laboratories (Color Health, Invitae/Labcorp, Ambry Genetics). Multiple reputable clinical laboratories have independently classified this variant as likely benign, meeting BP6 criteria for a reputable source reporting the variant as benign.

BP7Supporting

BP7 · supporting

NM_032043.3:c.2085G>A is a synonymous variant at codon 695 (p.Leu695=) in exon 14 of BRIP1. SpliceAI predicts no impact on splicing (all delta scores = 0.00; donor/acceptor gain/loss scores all at zero). The variant is not located in a highly conserved splice region. BP7 is met for a synonymous variant with no predicted effect on splicing.

Recorded classification: Likely benign

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BP4 supporting, BP6 supporting, BP7 supporting; combination = 3 supporting benign, which maps to Likely Benign.

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

Not recorded

gnomAD v4.1 allele counts were not recorded for this variant.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

No listed criterion applied

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 · BP4, BP7 → SpliceAI ↗

ClinVar submissions

3 reported laboratory submissions

3 Likely benign.

Applied · BP6 → ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

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.

26 criteria with recorded statuses: 3 met · 8 not met · 10 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

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

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_032043.3:c.2085G>A is a synonymous variant in exon 14 of BRIP1 encoding p.Leu695=, predicting no amino acid change.

SpliceAI predicts no impact on splicing (max delta score 0.00), supporting a benign interpretation (BP4_Supporting, BP7_Supporting).

This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, though absence from population databases does not independently support either benign or pathogenic interpretation for a synonymous variant.

ClinVar classifies this variant as Likely benign (VariationID 530367) based on submissions from three clinical diagnostic laboratories (BP6_Supporting).

No variant-specific functional data, segregation data, case-control studies, or de novo observations were identified in the literature. No paper reviewed directly mentions NM_032043.3:c.2085G>A.

Applying generic ACMG/AMP 2015 classification rules: BP6_Supporting + BP7_Supporting result in Likely Benign (at least two supporting benign criteria).

Met · 3

BP4 SupportingSpliceAI predicts no splicing impact for this synonymous variant (max delta score 0.00 across all acceptor and donor positions). REVEL and BayesDel do not provide scores for synonymous variants. The available computational evidence, while limited to splicing prediction, supports a benign interpretation. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score = 0.00
no predicted disruption of splicing.

Still missing

REVEL and BayesDel not applicable to synonymous variants
only SpliceAI available for in silico assessment.

Sources

spliceai ↗

BP6 SupportingClinVar reports NM_032043.3:c.2085G>A as Likely benign (VariationID 530367), based on submissions from three clinical diagnostic laboratories (Color Health, Invitae/Labcorp, Ambry Genetics). Multiple reputable clinical laboratories have independently classified this variant as likely benign, meeting BP6 criteria for a reputable source reporting the variant as benign. Details ▾Hide ▴

Evidence considered

ClinVar Likely benign classification (3 clinical laboratories): Color Health (SCV001347440)
Labcorp/Invitae (SCV000757640)
Ambry Genetics (SCV006208078).

Sources

clinvar ↗

BP7 SupportingNM_032043.3:c.2085G>A is a synonymous variant at codon 695 (p.Leu695=) in exon 14 of BRIP1. SpliceAI predicts no impact on splicing (all delta scores = 0.00; donor/acceptor gain/loss scores all at zero). The variant is not located in a highly conserved splice region. BP7 is met for a synonymous variant with no predicted effect on splicing. Details ▾Hide ▴

Evidence considered

Synonymous variant (p.Leu695=) at exon 14 position
SpliceAI max delta score = 0.00
no predicted alteration of native splice sites.

Sources

spliceai ↗

Not met · 8 · evaluated, threshold not reached

PS3 No well-established functional studies demonstrating a deleterious effect have been identified for this variant. The literature reviewed (PMID:25741868, PMID:31429903) contains no variant-specific functional data. Details ▾Hide ▴

Evidence considered

No functional studies identified in ClinVar submissions or literature review.

Still missing

No functional assays performed for this variant.

PM1 This synonymous variant is not located in a statistically significant mutational hotspot or a well-established functional domain without benign variation. Hotspot analysis returned negative. Details ▾Hide ▴

Evidence considered

Hotspot analysis: variant does not lie in a statistically significant hotspot.

PM2 While this variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, PM2 is not applied to synonymous variants with no predicted splice impact because the variant class (synonymous, predicted neutral by SpliceAI) explains its rarity and does not support a pathogenic interpretation. The absence from population databases is expected for rare neutral variants. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1
v4.1
and gnomAD-Canada
not applied due to synonymous variant class with no predicted splice impact.

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PP3 In silico tools do not predict a deleterious effect. REVEL and BayesDel scores are not available for this synonymous variant. SpliceAI predicts no splicing impact (max delta score 0.00). Multiple lines of computational evidence do not support pathogenicity. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score = 0.00
REVEL not found (synonymous)
BayesDel not found.

Sources

spliceai ↗

PP5 PP5 requires a reputable source to report the variant as pathogenic. ClinVar classifies NM_032043.3:c.2085G>A as Likely benign (VariationID 530367) based on three clinical laboratory submissions. No source classifies this variant as pathogenic. Details ▾Hide ▴

Evidence considered

ClinVar classification is Likely benign (3 clinical laboratories)
no reputable source reports this variant as pathogenic.

Sources

clinvar ↗

BA1 This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. BA1 requires an allele frequency >1% in population databases (non-VCEP threshold). The variant does not meet this threshold. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1
v4.1
and gnomAD-Canada.

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

BS1 This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. BS1 requires an allele frequency >0.3% in population databases (non-VCEP threshold). The variant does not meet this threshold. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1
v4.1
and gnomAD-Canada.

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PS5 PS5 is not a standard ACMG/AMP 2015 criterion. To the extent it is interpreted as a reputable source reporting the variant as pathogenic, no such evidence exists; ClinVar reports Likely benign, and no source has classified this variant as pathogenic. Details ▾Hide ▴

Evidence considered

ClinVar classification is Likely benign (VariationID 530367)
no source reports this variant as pathogenic.

Sources

clinvar ↗

Not assessed · 10 · no assessment recorded

PS2 No de novo data are available for this variant. PS2 requires confirmation of both maternity and paternity in a patient with disease and no family history. Details ▾Hide ▴

Evidence considered

No de novo observations identified in ClinVar submissions or literature.

Still missing

No de novo testing data available.

PS4 No case-control or case-series prevalence data are available for this variant. PS4 requires a statistically significant enrichment in affected individuals compared to controls. Details ▾Hide ▴

Evidence considered

No prevalence data identified in the literature.

Still missing

No case-control studies available.

PM6 No assumed de novo data are available for this variant. PM6 requires a de novo observation without confirmation of paternity and maternity. Details ▾Hide ▴

Evidence considered

No de novo observations identified.

Still missing

No de novo data available.

PP1 No co-segregation data are available for this variant. PP1 requires co-segregation with disease in multiple affected family members. Details ▾Hide ▴

Evidence considered

No segregation data identified in ClinVar submissions or literature.

Still missing

No family segregation data available.

PP4 No patient phenotype or family history data specific to this variant are available. PP4 requires the patient's phenotype or family history to be highly specific for a disease with a single genetic etiology. Details ▾Hide ▴

Evidence considered

No phenotype data available for variant carriers.

Still missing

No clinical phenotype data for variant carriers.

BS2 No data are available regarding observation of this variant in healthy adult individuals for a fully penetrant disorder. BS2 requires observation in a healthy adult homozygous or hemizygous individual for a fully penetrant early-onset disorder. Details ▾Hide ▴

Evidence considered

No healthy control data specific to this variant.

Still missing

No healthy adult carrier data available.

BS3 No well-established functional studies demonstrating no damaging effect have been identified for this variant. The literature reviewed contains no variant-specific functional data. Details ▾Hide ▴

Evidence considered

No functional data identified for this variant.

Still missing

No functional studies available for this variant.

BS4 No segregation data are available for this variant. BS4 requires lack of segregation with disease in affected family members. Details ▾Hide ▴

Evidence considered

No segregation data available.

Still missing

No family segregation data available.

BP2 No data are available regarding observation of this variant in trans with a pathogenic variant for a fully penetrant dominant disorder. Details ▾Hide ▴

Evidence considered

No phase data available.

Still missing

No phasing data with known pathogenic variants.

BP5 No data are available regarding an alternate molecular basis for disease in individuals carrying this variant. Details ▾Hide ▴

Evidence considered

No alternate molecular diagnosis data available.

Still missing

No data on alternate molecular diagnoses in carriers.

Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/ANM_032043.3:c.2085G>A is a synonymous variant (p.Leu695=), not a null variant (nonsense, frameshift, or canonical splice site). PVS1 is reserved for variants predicted to cause loss of function via transcript nonsense-mediated decay or truncation. Details ▾Hide ▴

Evidence considered

Synonymous variant
pvs1_variant_assessment confirms apply_generic_pvs1_framework=false.

Sources

pvs1_variant_assessment

PS1 N/AThis is a synonymous variant producing no amino acid change. PS1 requires the same amino acid change as a previously established pathogenic variant, which is not applicable to synonymous variants. Details ▾Hide ▴

Evidence considered

Synonymous variant (p.Leu695=)
no amino acid change.

PM5 N/AThis is a synonymous variant (p.Leu695=), not a missense change. PM5 requires a novel missense variant at the same amino acid residue as a known pathogenic missense variant. pm5_candidates.json confirms no eligible comparator candidates. Details ▾Hide ▴

Evidence considered

Synonymous variant
unable to parse missense residue context. PM5 candidate search returned no candidates.

Sources

pm5_candidates

PP2 N/APP2 applies to missense variants in genes with a low rate of benign missense variation and where missense is a common disease mechanism. This variant is synonymous (p.Leu695=), not missense. Details ▾Hide ▴

Evidence considered

Synonymous variant
PP2 is specific to missense variants.

BP1 N/ABP1 applies to missense variants in genes where only truncating variants cause disease. This variant is synonymous (p.Leu695=), not missense. Details ▾Hide ▴

Evidence considered

Synonymous variant
BP1 is specific to missense variants.

Identifiers

Gene: BRIP1
Transcript: NM_032043.3
Coding (HGVS c.): NM_032043.3:c.2085G>A
Protein (HGVS p.): NP_114432.2:p.(Leu695=)
GRCh38: chr17:61776413 C>T
GRCh37: chr17:59853774 C>T
ClinVar: 530367

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 Allele count data not recorded

gnomAD v2.1 Allele count data not recorded

gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +89 bp

0.000

SpliceAI acceptor gainat -219 bp

0.000

SpliceAI donor lossat -12 bp

0.000

SpliceAI donor gainat +27 bp

0.000

Pangolin splice lossmagnitude shown

-0.000

Pangolin splice gain

0.000

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta score = 0.00
no predicted disruption of splicing.

Still missing

REVEL and BayesDel not applicable to synonymous variants
only SpliceAI available for in silico assessment.

Sources

spliceai ↗

Evidence considered

Synonymous variant (p.Leu695=) at exon 14 position
SpliceAI max delta score = 0.00
no predicted alteration of native splice sites.

Sources

spliceai ↗

Evidence considered

SpliceAI max delta score = 0.00
REVEL not found (synonymous)
BayesDel not found.

Sources

spliceai ↗

Statement

In silico

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

7 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

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 ACMG/AMP variant interpretation. This paper defines the classification framework and does not discuss individual variants. NM_032043.3:c.2085G>A was not identified in this paper.
Does not name this variant
PMID 25741868 ↗
The emerging landscape of breast cancer susceptibility.

Stratton MR et al. · 2008

Review of emerging breast cancer susceptibility genes and risk alleles. Discusses BRCA1, BRCA2, and moderate-risk genes at a general level. NM_032043.3:c.2085G>A was not identified in this paper.
Does not name this variant
PMID 18163131 ↗
BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.

Adam MP et al. · 1993

GeneReviews chapter on BRCA1- and BRCA2-associated hereditary breast and ovarian cancer. Focuses on BRCA1/2; BRIP1 is not discussed. NM_032043.3:c.2085G>A was not identified in this paper.
Does not name this variant
PMID 20301425 ↗
Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version.

PDQ Cancer Genetics Editorial Board · 2002

PDQ cancer genetics summary covering general cancer predisposition syndromes. Does not discuss specific BRIP1 variants. NM_032043.3:c.2085G>A was not identified in this paper.
Does not name this variant
PMID 26389210 ↗
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement.

USPSTF recommendation statement on BRCA-related cancer risk assessment, genetic counseling, and testing. Focuses exclusively on BRCA1/2; BRIP1 is not mentioned. NM_032043.3:c.2085G>A was not identified in this paper.
Does not name this variant
PMID 31429903 ↗
PMID 31479213

No paper-specific finding is recorded.

PMID 31479213 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Sherloc refinement of ACMG-AMP variant classification criteria. Describes a classification framework and does not discuss individual variants. NM_032043.3:c.2085G>A was not identified in this paper.
Does not name this variant
PMID 28492532 ↗

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

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗

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

SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗

ClinVar 3 Likely benign 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

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely benign (3 clinical laboratories). (ClinVarID = 530367)

In silico

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

Functional

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

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.