BRCA1c.3700_3704delPathogenic

Print report

Variant interpretation report

BRCA1 c.3700_3704del, p.(Val1234GlnfsTer8)

NM_007294.4:c.3700_3704del NP_009225.1:p.(Val1234GlnfsTer8) View identifiers

Classification

Pathogenic

Variant description:

No variant summary was recorded for this case.

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

Pathogenic.A pathogenic classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About BRCA1

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 very strong (pathogenic) · 2 strong (pathogenic) · 2 supporting (pathogenic)
Expert rules: ClinGen BRCA1 VCEP v1.2.0
Other laboratories (ClinVar): 38 Pathogenic · 3 pathogenic
Pipeline record: 9 Jul 2026 · version 7.0.1

Evidence considered

View criteria

Applied evidence criteria

PVS1 (very strong): NM_007294.4:c.3700_3704del is a frameshift deletion in BRCA1 exon 10 (legacy exon 11), resulting in a premature termination codon (p.Val1234GlnfsTer8) predicted to undergo nonsense-mediated decay. Loss of function is an established disease mechanism for BRCA1. The ENIGMA BRCA1 specification (v1.2) assigns PVS1 at full strength for PTC variants in exon 10(11) per Table 4.
PM2 (supporting): The variant is absent from gnomAD v2.1 (non-cancer, exome) and present in gnomAD v4.1 at extremely low frequency (5/1,614,374 alleles; MAF 0.00031%; grpmax FAF 1.24e-06). This meets ENIGMA PM2_Supporting: absent from controls in an outbred population per gnomAD v2.1/v3.1 criteria.
PM5 (strong): This is a protein termination codon (PTC) variant in BRCA1 exon 10 (legacy exon 11), where multiple proven pathogenic PTC variants have been observed (e.g., c.5266dupC). ENIGMA Table 4 assigns PM5_Strong (PTC) for PTC variants in exon E10(11). This criterion captures the additional weight beyond PVS1 for a PTC in an exon with established pathogenic PTCs.
PP4 (strong): The variant's clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) is LR = 57.23 (LOG(LR) = 4.047, N_Probands = 10). This exceeds the PP4_Strong threshold of LR ≥18.7 and is based on personal and family cancer history data from multigene panel testing, indicating significant enrichment of a breast/ovarian cancer phenotype in carriers compared to non-carriers.
PP5 (supporting): Expert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Pathogenic.

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 ClinGen BRCA1 VCEP v1.2.0. 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: 5 Benign evidence criteria: 0

Pathogenic criteria applied · 5

PVS1Very strong

PVS1 · very strong

NM_007294.4:c.3700_3704del is a frameshift deletion in BRCA1 exon 10 (legacy exon 11), resulting in a premature termination codon (p.Val1234GlnfsTer8) predicted to undergo nonsense-mediated decay. Loss of function is an established disease mechanism for BRCA1. The ENIGMA BRCA1 specification (v1.2) assigns PVS1 at full strength for PTC variants in exon 10(11) per Table 4.

PM2Supporting

PM2 · supporting

The variant is absent from gnomAD v2.1 (non-cancer, exome) and present in gnomAD v4.1 at extremely low frequency (5/1,614,374 alleles; MAF 0.00031%; grpmax FAF 1.24e-06). This meets ENIGMA PM2_Supporting: absent from controls in an outbred population per gnomAD v2.1/v3.1 criteria.

PM5Strong

PM5 · strong

This is a protein termination codon (PTC) variant in BRCA1 exon 10 (legacy exon 11), where multiple proven pathogenic PTC variants have been observed (e.g., c.5266dupC). ENIGMA Table 4 assigns PM5_Strong (PTC) for PTC variants in exon E10(11). This criterion captures the additional weight beyond PVS1 for a PTC in an exon with established pathogenic PTCs.

PP4Strong

PP4 · strong

The variant's clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) is LR = 57.23 (LOG(LR) = 4.047, N_Probands = 10). This exceeds the PP4_Strong threshold of LR ≥18.7 and is based on personal and family cancer history data from multigene panel testing, indicating significant enrichment of a breast/ovarian cancer phenotype in carriers compared to non-carriers.

PP5Supporting

PP5 · supporting

Expert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Pathogenic.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Pathogenic

ENIGMA BRCA1/BRCA2 Specification v1.2.0 Table 3. The variant accumulates 1 Very Strong criterion (PVS1) and 2 Strong criteria (PM5_Strong, PP4_Strong), satisfying the pathogenic rule: 1 Very Strong + ≥1 Strong. Additionally, 2 Supporting criteria (PM2_Supporting, PP5_Supporting) provide further corroboration but are not required for this call.

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

5 / 1,614,174 alleles

gnomAD v4.1: 5 / 1,614,174 alleles. Recorded AF 3.09756e-06. Recorded homozygote count 0.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →

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

SpliceAI score

0.050 maximum delta

Recorded SpliceAI maximum delta score: 0.050. Refer to the recorded PP3/BP4 rationale for interpretation.

No listed criterion applied SpliceAI ↗

ClinVar submissions

41 reported laboratory submissions

38 Pathogenic · 3 pathogenic. ClinVar API review status: reviewed by expert panel.

Applied · PP5 → ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.

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 ClinGen BRCA1 VCEP v1.2.0, with the data and sources behind each one.

29 criteria with recorded statuses: 5 met · 8 not met · 0 not assessed · 16 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_007294.4:c.3700_3704del (p.Val1234GlnfsTer8) is a frameshift deletion in BRCA1 exon 10 that creates a premature termination codon, meeting PVS1 at very strong strength per ENIGMA Table 4 for PTC variants in E10(11).

The variant is absent from gnomAD v2.1 and present at extremely low frequency in gnomAD v4.1 (5/1,614,374 alleles; MAF 0.00031%; grpmax FAF=1.24e-06), meeting PM2_Supporting.

ENIGMA Table 4 assigns PM5_Strong (PTC) for protein termination codon variants in BRCA1 exon 10(11), an exon with multiple established pathogenic PTC variants.

Clinical-history likelihood ratio analysis from Li et al. 2020 (PMID:31853058) yields LR = 57.23 (N_Probands = 10), meeting PP4_Strong (LR ≥18.7), indicating significant enrichment of breast/ovarian cancer phenotype in carriers.

The variant has been classified as Pathogenic by the ENIGMA expert panel in ClinVar (ClinVar ID 37542) and has been observed as a recurrent founder mutation in multiple Central European populations.

Overall classification: Pathogenic under ENIGMA Table 3 rules (1 Very Strong + ≥1 Strong). Criteria met: PVS1 (Very Strong), PM5_Strong (PTC), PP4_Strong, PM2_Supporting.

Met · 5

PVS1 Very strongNM_007294.4:c.3700_3704del is a frameshift deletion in BRCA1 exon 10 (legacy exon 11), resulting in a premature termination codon (p.Val1234GlnfsTer8) predicted to undergo nonsense-mediated decay. Loss of function is an established disease mechanism for BRCA1. The ENIGMA BRCA1 specification (v1.2) assigns PVS1 at full strength for PTC variants in exon 10(11) per Table 4. Details ▾Hide ▴

Evidence considered

Frameshift deletion creating PTC at codon 1234 (p.Val1234GlnfsTer8)
Located in BRCA1 exon 10 (legacy exon 11)
within the large exon encoding aa 224-1366
ENIGMA Table 4 assigns PVS1 for PTC variants in E10(11)
BRCA1 loss of function is an established disease mechanism per ClinGen CSPEC

Sources

cspec ↗vcep_specifications_table4_v1_2_2024_11_18pvs1_gene_contextpvs1_variant_assessmentpvs1_generic_framework ↗

PM2 SupportingThe variant is absent from gnomAD v2.1 (non-cancer, exome) and present in gnomAD v4.1 at extremely low frequency (5/1,614,374 alleles; MAF 0.00031%; grpmax FAF 1.24e-06). This meets ENIGMA PM2_Supporting: absent from controls in an outbred population per gnomAD v2.1/v3.1 criteria. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 (non-cancer
exome)
gnomAD v4.1: 5/1
614
374 alleles (MAF 0.00031%)
grpmax FAF=1.24e-06
Absent from gnomAD-Canada v1.0
Highest subpopulation frequency: European non-Finnish AF=4.24e-06

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗cspec ↗

PM5 StrongThis is a protein termination codon (PTC) variant in BRCA1 exon 10 (legacy exon 11), where multiple proven pathogenic PTC variants have been observed (e.g., c.5266dupC). ENIGMA Table 4 assigns PM5_Strong (PTC) for PTC variants in exon E10(11). This criterion captures the additional weight beyond PVS1 for a PTC in an exon with established pathogenic PTCs. Details ▾Hide ▴

Evidence considered

ENIGMA Table 4
E10(11) PTC row: Column L = PM5_Strong (PTC)
Exon 10(11) contains well-established pathogenic PTC variants (founder c.5266dupC among others)

Sources

vcep_specifications_table4_v1_2_2024_11_18cspec ↗

PP4 StrongThe variant's clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) is LR = 57.23 (LOG(LR) = 4.047, N_Probands = 10). This exceeds the PP4_Strong threshold of LR ≥18.7 and is based on personal and family cancer history data from multigene panel testing, indicating significant enrichment of a breast/ovarian cancer phenotype in carriers compared to non-carriers. Details ▾Hide ▴

Evidence considered

LR = 57.23 from PMID:31853058 clinical-history model (N_Probands = 10)
Exceeds ENIGMA PP4_Strong threshold (LR ≥18.7)

Sources

PMID:31853058 ↗vcep_pmid_31853058_brca1_clinical_history_lrcspec ↗

PP5 SupportingExpert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Pathogenic. Details ▾Hide ▴

Evidence considered

ClinVar expert panel classification

Sources

clinvar ↗

Not met · 8 · evaluated, threshold not reached

PS4 PS4 requires a case-control study with p-value ≤0.05 and OR ≥4 (lower CI excludes 2.0). The variant has been observed in multiple affected families across population studies (29 families in Czech population, 7 families in German population), but no formal case-control analysis meeting ENIGMA statistical thresholds was identified for this specific variant. Details ▾Hide ▴

Evidence considered

Observed in 29/204 BRCA1-mutation-positive Czech families (Machackova 2008)
Observed in 7 German breast/ovarian cancer families (German Consortium 2002)
No formal case-control OR meeting ENIGMA PS4 thresholds (OR≥4
p≤0.05) available

Still missing

Formal case-control study with OR and p-value for this specific variant not available

Sources

PMID:18489799 ↗PMID:11802209 ↗

PP1 PP1 requires quantitative co-segregation analysis with LR ≥2.08. No co-segregation LR data was identified for this variant. While the variant has been observed in multiple families, no formal co-segregation likelihood ratio meeting ENIGMA thresholds is available in the evidence. Details ▾Hide ▴

Evidence considered

No quantitative co-segregation LR analysis available for this variant

Still missing

Formal co-segregation analysis with LR calculation not available

PP3 PP3 in ENIGMA applies to missense/in-frame variants in functional domains with BayesDel ≥0.28, or variants with predicted splicing impact (SpliceAI ≥0.2). This is a frameshift deletion. SpliceAI max delta score = 0.05, well below the 0.2 threshold. No computational evidence for additional splicing impact is present. The pathogenic effect is already captured by PVS1. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score = 0.05 (below PP3 threshold of 0.2)
REVEL/BayesDel not applicable to deletion variants

Sources

spliceai ↗

BA1 BA1 requires filter allele frequency (FAF) > 0.1% (0.001) in gnomAD. The grpmax FAF for this variant is 1.24e-06, far below the BA1 threshold. This variant is not present at a frequency consistent with a benign polymorphism. Details ▾Hide ▴

Evidence considered

gnomAD v4.1 grpmax FAF = 1.24e-06
far below BA1 threshold of 0.001

Sources

gnomad_v4 ↗cspec ↗

BS1 BS1_Supporting requires FAF > 0.00002 (0.002%) in gnomAD. The grpmax FAF is 1.24e-06 (0.000124%), which is below even the BS1_Supporting threshold. The variant is too rare in population databases to apply BS1 at any strength. Details ▾Hide ▴

Evidence considered

gnomAD v4.1 grpmax FAF = 1.24e-06
below BS1_Supporting threshold of 0.00002

Sources

gnomad_v4 ↗cspec ↗

BS2 BS2 requires documented absence of Fanconi Anemia features in homozygous or compound heterozygous individuals. No proband-level data reporting absence or presence of FA phenotype was available for this variant. Without specific clinical data, BS2 cannot be applied. Details ▾Hide ▴

Evidence considered

No proband-level data on Fanconi Anemia phenotype available

Still missing

Absence of FA phenotype cannot be confirmed without proband clinical data

BS4 BS4 requires quantitative lack-of-segregation analysis with LR ≤0.48. No segregation data showing absence of co-segregation was identified for this variant. On the contrary, the variant has been observed in multiple affected families, consistent with pathogenic segregation. Details ▾Hide ▴

Evidence considered

No evidence of lack of segregation
variant observed in multiple affected families

BP5 BP5 requires a combined likelihood ratio against pathogenicity (LR ≤0.48). The clinical-history LR for this variant is 57.23, which is strongly toward pathogenicity. BP5 is not applicable. Details ▾Hide ▴

Evidence considered

Clinical-history LR = 57.23
strongly pathogenic direction
inconsistent with BP5

Sources

PMID:31853058 ↗

Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴

PS1 N/APS1 applies to predicted missense substitutions where a previously classified pathogenic variant acts via the same amino acid change, or to exonic/intronic variants with the same predicted splicing impact. This variant is a frameshift deletion, not a missense substitution or splicing variant. Details ▾Hide ▴

No further detail was recorded.

PS2 VCEPPS2 (de novo) is listed as Not Applicable in the ENIGMA BRCA1 CSPEC. Details ▾Hide ▴

No further detail was recorded.

PS3 N/AThis is a null (frameshift) variant. The damaging effect on protein function is captured by PVS1. ENIGMA PS3 applies to missense variants with calibrated functional assay evidence per Table 9, which does not list this frameshift variant. No variant-specific functional assay is available or needed. Details ▾Hide ▴

No further detail was recorded.

PM1 VCEPPM1 is listed as Not Applicable in the ENIGMA BRCA1 CSPEC. Details ▾Hide ▴

No further detail was recorded.

PM3 N/APM3 is skipped per directive. Details ▾Hide ▴

No further detail was recorded.

PM4 VCEPPM4 is listed as Not Applicable in the ENIGMA BRCA1 CSPEC. Details ▾Hide ▴

No further detail was recorded.

PM6 VCEPPM6 is listed as Not Applicable in the ENIGMA BRCA1 CSPEC. Details ▾Hide ▴

No further detail was recorded.

PP2 VCEPPP2 is listed as Not Applicable in the ENIGMA BRCA1 CSPEC. Details ▾Hide ▴

No further detail was recorded.

BS3 N/AThis is a null (frameshift) variant. ENIGMA BS3 applies to missense variants with calibrated functional assay evidence per Table 9, which does not include this frameshift variant. The loss-of-function effect is already captured by PVS1. Details ▾Hide ▴

No further detail was recorded.

BP1 N/ABP1 applies to silent substitutions, missense, or in-frame insertion/deletion variants outside clinically important functional domains with no splicing predicted (SpliceAI ≤0.1). This is a frameshift deletion, not covered by BP1. Details ▾Hide ▴

No further detail was recorded.

BP2 VCEPBP2 is listed as Not Applicable in the ENIGMA BRCA1 CSPEC. Details ▾Hide ▴

No further detail was recorded.

BP3 VCEPBP3 is listed as Not Applicable in the ENIGMA BRCA1 CSPEC. Details ▾Hide ▴

No further detail was recorded.

BP4 N/ABP4 applies to missense or in-frame insertion/deletion variants inside clinically important functional domains with no predicted impact (BayesDel ≤0.15 and SpliceAI ≤0.1). This is a frameshift deletion, not covered by BP4. Details ▾Hide ▴

No further detail was recorded.

BP6 VCEPBP6 is listed as Not Applicable in the ENIGMA BRCA1 CSPEC. Details ▾Hide ▴

No further detail was recorded.

BP7 N/ABP7 applies to intronic and silent variants, or missense/in-frame variants outside functional domains, with mRNA assay showing no splicing impact. This is a frameshift deletion, not covered by BP7. Details ▾Hide ▴

No further detail was recorded.

PS5 N/APS5 is not defined in the ENIGMA BRCA1 CSPEC and is not assessed. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: BRCA1
Transcript: NM_007294.4
Coding (HGVS c.): NM_007294.4:c.3700_3704del
Protein (HGVS p.): NP_009225.1:p.(Val1234GlnfsTer8)
GRCh38: chr17:43091826 GTTTAC>G
GRCh37: chr17:41243843 GTTTAC>G
ClinVar: 37542

Gene diagram

Every interpreted variant in BRCA1, mapped onto the exon structure of NM_007294.4. Select a row to find it on the plot.

BRCA1NM_007294.4

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 BRCA1 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 5 / 1,614,174 alleles AF 3.1e-06 · 0 homozygotes · FAF 1.24e-06

gnomAD v2.1 Allele count data not recorded

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 3.1e-06 · 5 / 1,614,174 alleles · 0 hom · FAF 1.2e-06

European (non-Finnish)5 / 1,180,032

4.2e-06

0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 3.09756e-06; MAF= 0.00031%, 5/1614174 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.23717e-06; MAF= 0.00042%, 5/1180032 alleles, homozygotes = 0); grpmax FAF= 1.24e-06.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat -323 bp

0.010

SpliceAI acceptor gainat -193 bp

0.040

SpliceAI donor lossat +11 bp

0.050

SpliceAI donor gainat -114 bp

0.010

Pangolin splice lossmagnitude shown

-0.100

Pangolin splice gain

0.020

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta score = 0.05 (below PP3 threshold of 0.2)
REVEL/BayesDel not applicable to deletion variants

Sources

spliceai ↗

No further detail was recorded.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05).

8 paper records listed. 2 cited in the classification.

Cited in the classification

Spectrum and characterisation of BRCA1 and BRCA2 deleterious mutations in high-risk Czech patients with breast and/or ovarian cancer.

Identified c.3700_3704del5 (NM_007294.4:c.3700_3704del) as one of three BRCA1 founder mutations in the Czech population, detected in 29 of 204 (14.2%) BRCA1-mutation-positive families. Described as a frameshift mutation leading to p.Val1234GlnfsX8.
→ PM5 Names this variant
PMID 18489799 ↗
Source detail

The BRCA1 c.3700_3704del5 mutation is a frequent mutation in Germany. Three BRCA1 Czech founder mutations (p.Cys61Gly, c.3700_3704del5, and c.5266dupC) accounted for 9.8%, 14.2% and 36.8% of the BRCA1 mutations identified, respectively.

Location Table 1 (BRCA1 mutations); Results, Discussion (founder mutations section)
Li et al. 2020 BRCA1/2 clinical-history likelihood-ratio model

Li et al. 2020 clinical-history likelihood-ratio model. The variant c.3700_3704delGTAAA (NM_007294.4:c.3700_3704del) has a LOG(LR) of 4.047 (LR = 57.23) based on 10 probands, providing strong evidence toward pathogenicity from personal and family cancer history.
→ PP4 Names this variant
PMID 31853058 ↗
Source detail

c.3700_3704delGTAAA: LOG(LR) = 4.047027111053467, LR = 57.22707417000815, N_Probands = 10

Location MOESM2 clinical-history LR spreadsheet (PMID_31853058_BRCA1_clinical_history_LR.xlsx)

Other recorded publications

Tumorigenesis in mice carrying a truncating Brca1 mutation.

Describes tumorigenesis in mice carrying a truncating Brca1 mutation (Brca1tr) that eliminates the C-terminal half. This is a mouse model study using an engineered truncation, not the human NM_007294.4:c.3700_3704del variant.
Does not name this variant
PMID 11358863 ↗
The cancer connection: BRCA1 and BRCA2 tumor suppression in mice and humans.

Review article on BRCA1 and BRCA2 tumor suppression in mice and humans. Discusses gene-level mechanisms without mention of the specific variant NM_007294.4:c.3700_3704del.
Does not name this variant
PMID 12483515 ↗
Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation.

Review of BRCA1 and BRCA2 roles in homologous recombination, DNA replication fidelity, and cellular response to ionizing radiation. No mention of NM_007294.4:c.3700_3704del.
Does not name this variant
PMID 12947386 ↗
BRCA1 16 years later: risk-associated BRCA1 mutations and their functional implications.

Review of BRCA1 mutations and their functional implications 16 years after gene discovery. Discusses risk-associated mutations at gene level without mention of NM_007294.4:c.3700_3704del.
Does not name this variant
PMID 20608970 ↗
Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population.

Meindl A et al. · 2002

Identified 3819del5bp (BIC nomenclature for c.3700_3704del) in 7 of 302 German breast/ovarian cancer families with deleterious BRCA1/2 mutations, confirming it is a recurrent mutation in the German population.
Names this variant
PMID 11802209 ↗
Quoted passage
3819del5bp 1242X FS y 7 3 3 1 11
Table 1 (BRCA1 mutation list), line 470; referred to as 3819del5bp, exon 11, FS (frameshift), protein 1242X
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

Borg A et al. · 2010

WECARE study characterizing BRCA1/2 deleterious mutations and VUS in contralateral and unilateral breast cancer. NM_007294.4:c.3700_3704del was not identified in the full text of this paper.
Does not name this variant
PMID 20104584 ↗
Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients.

Study of germline BRCA1/2 variation in over 30,000 Chinese hereditary breast and ovarian cancer patients. NM_007294.4:c.3700_3704del was not identified in the full text of this paper.
Does not name this variant
PMID 30702160 ↗

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

gnomAD v4.1 5 / 1,614,174 recorded alleles Open source ↗

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

SpliceAI Lookup Recorded maximum delta 0.050 Open source ↗

ClinVar 38 Pathogenic · 3 pathogenic 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 ↗

ClinGen CSpec Captured ClinGen CSpec 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

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Pathogenic (38 clinical laboratories) and as pathogenic (3 clinical laboratories) and as Pathogenic by Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) (expert panel). (ClinVarID = 37542)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05).

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.

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.