2-214807822-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000465.4(BARD1):​c.158+1590C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,178 control chromosomes in the GnomAD database, including 42,464 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.75 ( 42464 hom., cov: 33)

Consequence

BARD1
NM_000465.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08
Variant links:
Genes affected
BARD1 (HGNC:952): (BRCA1 associated RING domain 1) This gene encodes a protein which interacts with the N-terminal region of BRCA1. In addition to its ability to bind BRCA1 in vivo and in vitro, it shares homology with the 2 most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes. This protein also contains 3 tandem ankyrin repeats. The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. This protein may be the target of oncogenic mutations in breast or ovarian cancer. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BARD1NM_000465.4 linkc.158+1590C>A intron_variant ENST00000260947.9 NP_000456.2 Q99728-1A0AVN2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BARD1ENST00000260947.9 linkc.158+1590C>A intron_variant 1 NM_000465.4 ENSP00000260947.4 Q99728-1

Frequencies

GnomAD3 genomes
AF:
0.746
AC:
113501
AN:
152060
Hom.:
42413
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.734
Gnomad AMI
AF:
0.740
Gnomad AMR
AF:
0.814
Gnomad ASJ
AF:
0.724
Gnomad EAS
AF:
0.849
Gnomad SAS
AF:
0.743
Gnomad FIN
AF:
0.765
Gnomad MID
AF:
0.756
Gnomad NFE
AF:
0.730
Gnomad OTH
AF:
0.737
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.747
AC:
113608
AN:
152178
Hom.:
42464
Cov.:
33
AF XY:
0.750
AC XY:
55811
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.734
Gnomad4 AMR
AF:
0.815
Gnomad4 ASJ
AF:
0.724
Gnomad4 EAS
AF:
0.849
Gnomad4 SAS
AF:
0.744
Gnomad4 FIN
AF:
0.765
Gnomad4 NFE
AF:
0.730
Gnomad4 OTH
AF:
0.740
Alfa
AF:
0.727
Hom.:
69481
Bravo
AF:
0.750
Asia WGS
AF:
0.790
AC:
2743
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.83
DANN
Benign
0.60

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: rs6435862; hg19: chr2-215672546; API