chr2-214761868-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000465.4(BARD1):​c.1568+5614G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,126 control chromosomes in the GnomAD database, including 47,750 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 0.79 ( 47750 hom., cov: 32)

Consequence

BARD1
NM_000465.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0950

Publications

2 publications found
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]
BARD1 Gene-Disease associations (from GenCC):
  • breast cancer
    Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
  • hereditary breast carcinoma
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
  • familial ovarian cancer
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • hereditary nonpolyposis colon cancer
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BARD1NM_000465.4 linkc.1568+5614G>A intron_variant Intron 6 of 10 ENST00000260947.9 NP_000456.2 Q99728-1A0AVN2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BARD1ENST00000260947.9 linkc.1568+5614G>A intron_variant Intron 6 of 10 1 NM_000465.4 ENSP00000260947.4 Q99728-1

Frequencies

GnomAD3 genomes
AF:
0.787
AC:
119642
AN:
152008
Hom.:
47726
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.666
Gnomad AMI
AF:
0.753
Gnomad AMR
AF:
0.776
Gnomad ASJ
AF:
0.820
Gnomad EAS
AF:
0.581
Gnomad SAS
AF:
0.828
Gnomad FIN
AF:
0.854
Gnomad MID
AF:
0.741
Gnomad NFE
AF:
0.864
Gnomad OTH
AF:
0.789
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.787
AC:
119717
AN:
152126
Hom.:
47750
Cov.:
32
AF XY:
0.785
AC XY:
58411
AN XY:
74364
show subpopulations
African (AFR)
AF:
0.666
AC:
27639
AN:
41472
American (AMR)
AF:
0.776
AC:
11871
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.820
AC:
2843
AN:
3466
East Asian (EAS)
AF:
0.582
AC:
3010
AN:
5174
South Asian (SAS)
AF:
0.828
AC:
3983
AN:
4812
European-Finnish (FIN)
AF:
0.854
AC:
9042
AN:
10590
Middle Eastern (MID)
AF:
0.745
AC:
219
AN:
294
European-Non Finnish (NFE)
AF:
0.864
AC:
58769
AN:
68006
Other (OTH)
AF:
0.784
AC:
1656
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1232
2463
3695
4926
6158
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
866
1732
2598
3464
4330
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.818
Hom.:
24928
Bravo
AF:
0.766
Asia WGS
AF:
0.694
AC:
2414
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
2.1
DANN
Benign
0.18
PhyloP100
0.095
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs6751923; hg19: chr2-215626592; API