Genetic Variant BARD1:c.1314+238G>A (chr2-214780322-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000465.4(BARD1):c.1314+238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,062 control chromosomes in the GnomAD database, including 39,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.71 ( 39357 hom., cov: 32)

Consequence

BARD1
NM_000465.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0480

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 2-214780322-C-T is Benign according to our data. Variant chr2-214780322-C-T is described in ClinVar as [Benign]. Clinvar id is 1280386.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BARD1	NM_000465.4 link	c.1314+238G>A		intron_variant	Intron 4 of 10	ENST00000260947.9	NP_000456.2	Q99728-1A0AVN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9 link	c.1314+238G>A		intron_variant	Intron 4 of 10	1	NM_000465.4	ENSP00000260947.4		Q99728-1

Frequencies

GnomAD3 genomes

AF:

0.715

AC:

108577

AN:

151944

Hom.:

39336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.758

Gnomad AMR

AF:

0.718

Gnomad ASJ

AF:

0.752

Gnomad EAS

AF:

0.793

Gnomad SAS

AF:

0.687

Gnomad FIN

AF:

0.857

Gnomad MID

AF:

0.755

Gnomad NFE

AF:

0.761

Gnomad OTH

AF:

0.717

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.714

AC:

108645

AN:

152062

Hom.:

39357

Cov.:

AF XY:

0.720

AC XY:

53509

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.589

AC:

24401

AN:

41434

American (AMR)

AF:

0.718

AC:

10961

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.752

AC:

2607

AN:

3468

East Asian (EAS)

AF:

0.792

AC:

4094

AN:

5166

South Asian (SAS)

AF:

0.688

AC:

3319

AN:

4822

European-Finnish (FIN)

AF:

0.857

AC:

9099

AN:

10612

Middle Eastern (MID)

AF:

0.764

AC:

223

AN:

292

European-Non Finnish (NFE)

AF:

0.761

AC:

51730

AN:

67982

Other (OTH)

AF:

0.720

AC:

1520

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1565

3130

4695

6260

7825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.743

Hom.:

159732

Bravo

AF:

0.697

Asia WGS

AF:

0.733

AC:

2546

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 22, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.4

(source)

DANN

Benign

0.71

PhyloP100

-0.048

Mutation Taster

=100/0

polymorphism (auto)

(source)

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 for variant 2:214780322 C>T . It may be empty.

chr2-214780322-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over