17-43097346-TAA-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_007294.4(BRCA1):​c.548-58del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,330,490 control chromosomes in the GnomAD database, including 75,741 homozygotes. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.30 ( 7389 hom., cov: 0)
Exomes 𝑓: 0.33 ( 68352 hom. )

Consequence

BRCA1
NM_007294.4 intron

Scores

Not classified

Clinical Significance

Benign reviewed by expert panel U:2B:9

Conservation

PhyloP100: 0.898
Variant links:
Genes affected
BRCA1 (HGNC:1100): (BRCA1 DNA repair associated) This gene encodes a 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2020]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 17-43097346-TA-T is Benign according to our data. Variant chr17-43097346-TA-T is described in ClinVar as [Benign]. Clinvar id is 125889.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43097346-TA-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BRCA1NM_007294.4 linkuse as main transcriptc.548-58del intron_variant ENST00000357654.9 NP_009225.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BRCA1ENST00000357654.9 linkuse as main transcriptc.548-58del intron_variant 1 NM_007294.4 ENSP00000350283 P4P38398-1

Frequencies

GnomAD3 genomes
AF:
0.300
AC:
45538
AN:
151888
Hom.:
7387
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.180
Gnomad AMI
AF:
0.285
Gnomad AMR
AF:
0.319
Gnomad ASJ
AF:
0.349
Gnomad EAS
AF:
0.369
Gnomad SAS
AF:
0.492
Gnomad FIN
AF:
0.405
Gnomad MID
AF:
0.339
Gnomad NFE
AF:
0.330
Gnomad OTH
AF:
0.321
GnomAD4 exome
AF:
0.332
AC:
390779
AN:
1178484
Hom.:
68352
AF XY:
0.338
AC XY:
202633
AN XY:
599366
show subpopulations
Gnomad4 AFR exome
AF:
0.172
Gnomad4 AMR exome
AF:
0.314
Gnomad4 ASJ exome
AF:
0.356
Gnomad4 EAS exome
AF:
0.351
Gnomad4 SAS exome
AF:
0.497
Gnomad4 FIN exome
AF:
0.396
Gnomad4 NFE exome
AF:
0.317
Gnomad4 OTH exome
AF:
0.329
GnomAD4 genome
AF:
0.300
AC:
45545
AN:
152006
Hom.:
7389
Cov.:
0
AF XY:
0.307
AC XY:
22773
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.180
Gnomad4 AMR
AF:
0.319
Gnomad4 ASJ
AF:
0.349
Gnomad4 EAS
AF:
0.369
Gnomad4 SAS
AF:
0.492
Gnomad4 FIN
AF:
0.405
Gnomad4 NFE
AF:
0.330
Gnomad4 OTH
AF:
0.325
Alfa
AF:
0.306
Hom.:
900
Bravo
AF:
0.282
Asia WGS
AF:
0.406
AC:
1410
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Uncertain:2Benign:9
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 1 Uncertain:1Benign:3
Benign, reviewed by expert panelcurationEvidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)Jan 12, 2015Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.33 (Asian), 0.13 (African), 0.35 (European), derived from 1000 genomes (2012-04-30). -
Benign, no assertion criteria providedclinical testingSharing Clinical Reports Project (SCRP)Mar 15, 2011- -
Benign, no assertion criteria providedclinical testingBreast Cancer Information Core (BIC) (BRCA1)Feb 20, 2004- -
Uncertain significance, no assertion criteria providedclinical testingBreast Cancer Information Core (BIC) (BRCA1)Mar 02, 2011- -
not specified Benign:3
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Benign, criteria provided, single submitterclinical testingGeneKor MSANov 01, 2017- -
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Uncertain significance, no assertion criteria providedclinical testingDepartment of Pathology and Laboratory Medicine, Sinai Health System-- -
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitterclinical testingColor Diagnostics, LLC DBA Color HealthMar 05, 2015- -
Hereditary breast ovarian cancer syndrome Benign:1
Benign, criteria provided, single submitterclinical testingNational Health Laboratory Service, Universitas Academic Hospital and University of the Free StateNov 16, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs8176144; hg19: chr17-41249363; API