chr2-214767468-G-A

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.1568+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,606,412 control chromosomes in the GnomAD database, including 96,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9520 hom., cov: 32)

Exomes 𝑓: 0.34 ( 87377 hom. )

Consequence

BARD1
NM_000465.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.295

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=-0.81).

BP6

Variant 2-214767468-G-A is Benign according to our data. Variant chr2-214767468-G-A is described in ClinVar as Benign. ClinVar VariationId is 256214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.389 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.1568+14C>T	intron	N/A	NP_000456.2	Q99728-1
BARD1	NM_001282543.2		c.1511+14C>T	intron	N/A	NP_001269472.1	Q99728-2
BARD1	NM_001282545.2		c.216-14913C>T	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.1568+14C>T	intron	N/A	ENSP00000260947.4	Q99728-1
BARD1	ENST00000617164.5	TSL:1	c.1511+14C>T	intron	N/A	ENSP00000480470.1	Q99728-2
BARD1	ENST00000613706.5	TSL:1	c.1160+14C>T	intron	N/A	ENSP00000484976.2	A0A087X2H0

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53226

AN:

151760

Hom.:

9506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.404

Gnomad FIN

AF:

0.452

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.362

GnomAD2 exomes

AF:

0.357

AC:

89442

AN:

250632

AF XY:

0.359

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.287

Gnomad ASJ exome

AF:

0.392

Gnomad EAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.452

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.344

AC:

500769

AN:

1454534

Hom.:

87377

Cov.:

AF XY:

0.346

AC XY:

250816

AN XY:

724016

show subpopulations

African (AFR)

AF:

0.341

AC:

11361

AN:

33290

American (AMR)

AF:

0.290

AC:

12973

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

9970

AN:

26056

East Asian (EAS)

AF:

0.358

AC:

14183

AN:

39646

South Asian (SAS)

AF:

0.397

AC:

34209

AN:

86066

European-Finnish (FIN)

AF:

0.455

AC:

24269

AN:

53310

Middle Eastern (MID)

AF:

0.357

AC:

2056

AN:

5756

European-Non Finnish (NFE)

AF:

0.336

AC:

370942

AN:

1105584

Other (OTH)

AF:

0.346

AC:

20806

AN:

60142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

15558

31116

46674

62232

77790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11894

23788

35682

47576

59470

<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:

0.351

AC:

53277

AN:

151878

Hom.:

9520

Cov.:

AF XY:

0.356

AC XY:

26462

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.346

AC:

14333

AN:

41418

American (AMR)

AF:

0.304

AC:

4648

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1369

AN:

3470

East Asian (EAS)

AF:

0.373

AC:

1917

AN:

5140

South Asian (SAS)

AF:

0.404

AC:

1945

AN:

4812

European-Finnish (FIN)

AF:

0.452

AC:

4755

AN:

10524

Middle Eastern (MID)

AF:

0.408

AC:

119

AN:

292

European-Non Finnish (NFE)

AF:

0.342

AC:

23215

AN:

67936

Other (OTH)

AF:

0.362

AC:

760

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1797

3594

5392

7189

8986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.342

Hom.:

28871

Bravo

AF:

0.334

Asia WGS

AF:

0.374

AC:

1299

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)

not specified (2)

Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

(source)

DANN

Benign

0.79

PhyloP100

-0.29

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