Variant 2-214809366-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000465.4(BARD1):c.158+46A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,606,874 control chromosomes in the GnomAD database, including 414,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41457 hom., cov: 33)

Exomes 𝑓: 0.71 ( 372658 hom. )

Consequence

BARD1
NM_000465.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.191

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-214809366-T-G is Benign according to our data. Variant chr2-214809366-T-G is described in ClinVar as [Benign]. Clinvar id is 1174423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BARD1	NM_000465.4 linkuse as main transcript	c.158+46A>C		intron_variant		ENST00000260947.9	NP_000456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9 linkuse as main transcript	c.158+46A>C		intron_variant		1	NM_000465.4	ENSP00000260947	P2	Q99728-1

Frequencies

GnomAD3 genomes

AF:

0.737

AC:

112103

AN:

152042

Hom.:

41393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.760

Gnomad AMI

AF:

0.686

Gnomad AMR

AF:

0.783

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.667

Gnomad FIN

AF:

0.763

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.721

GnomAD3 exomes

AF:

0.739

AC:

172011

AN:

232616

Hom.:

64018

AF XY:

0.730

AC XY:

93610

AN XY:

128176

show subpopulations

Gnomad AFR exome

AF:

0.766

Gnomad AMR exome

AF:

0.820

Gnomad ASJ exome

AF:

0.715

Gnomad EAS exome

AF:

0.812

Gnomad SAS exome

AF:

0.665

Gnomad FIN exome

AF:

0.783

Gnomad NFE exome

AF:

0.713

Gnomad OTH exome

AF:

0.719

GnomAD4 exome

AF:

0.715

AC:

1039451

AN:

1454714

Hom.:

372658

Cov.:

AF XY:

0.712

AC XY:

515331

AN XY:

723318

show subpopulations

Gnomad4 AFR exome

AF:

0.761

Gnomad4 AMR exome

AF:

0.815

Gnomad4 ASJ exome

AF:

0.711

Gnomad4 EAS exome

AF:

0.792

Gnomad4 SAS exome

AF:

0.668

Gnomad4 FIN exome

AF:

0.784

Gnomad4 NFE exome

AF:

0.707

Gnomad4 OTH exome

AF:

0.718

GnomAD4 genome

AF:

0.738

AC:

112225

AN:

152160

Hom.:

41457

Cov.:

AF XY:

0.740

AC XY:

55050

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.760

Gnomad4 AMR

AF:

0.784

Gnomad4 ASJ

AF:

0.722

Gnomad4 EAS

AF:

0.805

Gnomad4 SAS

AF:

0.669

Gnomad4 FIN

AF:

0.763

Gnomad4 NFE

AF:

0.711

Gnomad4 OTH

AF:

0.725

Alfa

AF:

0.716

Hom.:

9773

Bravo

AF:

0.741

Asia WGS

AF:

0.741

AC:

2575

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.2

DANN

Benign

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over