Genetic Variant BARD1:c.159-2550G>A (chr2-214799667-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000465.4(BARD1):c.159-2550G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,500 control chromosomes in the GnomAD database, including 5,543 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 0.26 ( 5543 hom., cov: 32)

Consequence

BARD1
NM_000465.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.42

Publications

10 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

BARD1 links:

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BARD1	NM_000465.4 link	c.159-2550G>A		intron_variant	Intron 1 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.159-2550G>A		intron_variant	Intron 1 of 10	1	NM_000465.4	ENSP00000260947.4		Q99728-1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39868

AN:

151384

Hom.:

5530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.0495

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.238

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

GnomAD4 genome

AF:

0.263

AC:

39914

AN:

151500

Hom.:

5543

Cov.:

AF XY:

0.260

AC XY:

19231

AN XY:

74072

show subpopulations

African (AFR)

AF:

0.359

AC:

14710

AN:

40944

American (AMR)

AF:

0.252

AC:

3843

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

515

AN:

3466

East Asian (EAS)

AF:

0.0494

AC:

256

AN:

5178

South Asian (SAS)

AF:

0.177

AC:

852

AN:

4826

European-Finnish (FIN)

AF:

0.202

AC:

2140

AN:

10582

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16799

AN:

67974

Other (OTH)

AF:

0.235

AC:

494

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1497

2994

4490

5987

7484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.247

Hom.:

15170

Bravo

AF:

0.269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

(source)

DANN

Benign

0.46

PhyloP100

-1.4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over