2-214728557-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000465.4(BARD1):​c.*119G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00045 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BARD1
NM_000465.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.866
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 -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 2-214728557-C-T is Benign according to our data. Variant chr2-214728557-C-T is described in ClinVar as [Benign]. Clinvar id is 801877.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 235 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BARD1NM_000465.4 linkuse as main transcriptc.*119G>A 3_prime_UTR_variant 11/11 ENST00000260947.9 NP_000456.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BARD1ENST00000260947.9 linkuse as main transcriptc.*119G>A 3_prime_UTR_variant 11/111 NM_000465.4 ENSP00000260947 P2Q99728-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
30
AN:
120766
Hom.:
0
Cov.:
30
FAILED QC
Gnomad AFR
AF:
0.0000927
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000853
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00298
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000174
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000452
AC:
235
AN:
520124
Hom.:
0
Cov.:
10
AF XY:
0.000482
AC XY:
127
AN XY:
263462
show subpopulations
Gnomad4 AFR exome
AF:
0.000480
Gnomad4 AMR exome
AF:
0.000559
Gnomad4 ASJ exome
AF:
0.000233
Gnomad4 EAS exome
AF:
0.000369
Gnomad4 SAS exome
AF:
0.00143
Gnomad4 FIN exome
AF:
0.000482
Gnomad4 NFE exome
AF:
0.000367
Gnomad4 OTH exome
AF:
0.000657
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000248
AC:
30
AN:
120806
Hom.:
0
Cov.:
30
AF XY:
0.000209
AC XY:
12
AN XY:
57358
show subpopulations
Gnomad4 AFR
AF:
0.0000925
Gnomad4 AMR
AF:
0.0000852
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00298
Gnomad4 NFE
AF:
0.000174
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Familial cancer of breast Benign:1
Benign, criteria provided, single submitterclinical testingMendelicsMay 28, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
1.4
DANN
Benign
0.40

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: rs1378645134; hg19: chr2-215593281; API