2-214769331-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000465.4(BARD1):c.1315-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,588,134 control chromosomes in the GnomAD database, including 108,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10615 hom., cov: 33)

Exomes 𝑓: 0.37 ( 98114 hom. )

Consequence

BARD1
NM_000465.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.126

Publications

12 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):

BARD1-related cancer predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
breast cancer
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
hereditary breast carcinoma
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

BARD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-214769331-C-T is Benign according to our data. Variant chr2-214769331-C-T is described in ClinVar as Benign. ClinVar VariationId is 256213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000465.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BARD1	NM_000465.4	MANE Select	c.1315-19G>A	intron	N/A	NP_000456.2	Q99728-1
BARD1	NM_001282543.2		c.1258-19G>A	intron	N/A	NP_001269472.1	Q99728-2
BARD1	NM_001282545.2		c.216-16776G>A	intron	N/A	NP_001269474.1	C9IYG1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BARD1	ENST00000260947.9	TSL:1 MANE Select	c.1315-19G>A	intron	N/A	ENSP00000260947.4	Q99728-1
BARD1	ENST00000617164.5	TSL:1	c.1258-19G>A	intron	N/A	ENSP00000480470.1	Q99728-2
BARD1	ENST00000613706.5	TSL:1	c.907-19G>A	intron	N/A	ENSP00000484976.2	A0A087X2H0

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56414

AN:

151866

Hom.:

10597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.468

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.379

GnomAD2 exomes

AF:

0.373

AC:

93106

AN:

249378

AF XY:

0.376

show subpopulations

Gnomad AFR exome

AF:

0.375

Gnomad AMR exome

AF:

0.294

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.469

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.355

GnomAD4 exome

AF:

0.368

AC:

528824

AN:

1436148

Hom.:

98114

Cov.:

AF XY:

0.370

AC XY:

264796

AN XY:

716104

show subpopulations

African (AFR)

AF:

0.369

AC:

12134

AN:

32886

American (AMR)

AF:

0.298

AC:

13281

AN:

44574

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

10551

AN:

25950

East Asian (EAS)

AF:

0.358

AC:

14140

AN:

39454

South Asian (SAS)

AF:

0.405

AC:

34706

AN:

85654

European-Finnish (FIN)

AF:

0.472

AC:

25150

AN:

53312

Middle Eastern (MID)

AF:

0.385

AC:

2206

AN:

5724

European-Non Finnish (NFE)

AF:

0.363

AC:

394878

AN:

1089090

Other (OTH)

AF:

0.366

AC:

21778

AN:

59504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14541

29081

43622

58162

72703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12442

24884

37326

49768

62210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.372

AC:

56470

AN:

151986

Hom.:

10615

Cov.:

AF XY:

0.377

AC XY:

27978

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.372

AC:

15407

AN:

41452

American (AMR)

AF:

0.319

AC:

4870

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

1446

AN:

3464

East Asian (EAS)

AF:

0.372

AC:

1926

AN:

5180

South Asian (SAS)

AF:

0.409

AC:

1965

AN:

4810

European-Finnish (FIN)

AF:

0.468

AC:

4929

AN:

10536

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.364

AC:

24759

AN:

67964

Other (OTH)

AF:

0.379

AC:

800

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1860

3720

5581

7441

9301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.308

Hom.:

1330

Bravo

AF:

0.354

Asia WGS

AF:

0.377

AC:

1312

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial cancer of breast (3)

Hereditary cancer-predisposing syndrome (2)

not provided (2)

Hereditary breast ovarian cancer syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

(source)

DANN

Benign

0.73

PhyloP100

0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over