dbSNP rs7190458: BCAR1:p.Leu787Leu (chr16-75229763-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014567.5(BCAR1):c.2361C>T(p.Leu787Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 1,613,400 control chromosomes in the GnomAD database, including 4,010 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 0.10 ( 1482 hom., cov: 33)

Exomes 𝑓: 0.046 ( 2528 hom. )

Consequence

BCAR1
NM_014567.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.883

Publications

54 publications found

Variant links:

Genes affected

BCAR1 (HGNC:971): (BCAR1 scaffold protein, Cas family member) The protein encoded by this gene is a member of the Crk-associated substrate (CAS) family of scaffold proteins, characterized by the presence of multiple protein-protein interaction domains and many serine and tyrosine phosphorylation sites. The encoded protein contains a Src-homology 3 (SH3) domain, a proline-rich domain, a substrate domain which contains 15 repeat of the YxxP consensus phosphorylation motif for Src family kinases, a serine-rich domain, and a bipartite Src-binding domain, which can bind both SH2 and SH3 domains. This adaptor protein functions in multiple cellular pathways, including in cell motility, apoptosis and cell cycle control. Dysregulation of this gene can have a wide range of effects, affecting different pathways, including cardiac development, vascular smooth muscle cells, liver and kidney function, endothelial migration, and cancer. [provided by RefSeq, Sep 2017]

BCAR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP7

Synonymous conserved (PhyloP=0.883 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAR1	NM_014567.5 link	c.2361C>T	p.Leu787Leu	synonymous_variant	Exon 7 of 7	ENST00000162330.10	NP_055382.2	P56945-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAR1	ENST00000162330.10 link	c.2361C>T	p.Leu787Leu	synonymous_variant	Exon 7 of 7	1	NM_014567.5	ENSP00000162330.5		P56945-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15579

AN:

152180

Hom.:

1474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.0798

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.0298

Gnomad SAS

AF:

0.00930

Gnomad FIN

AF:

0.0449

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0438

Gnomad OTH

AF:

0.0923

GnomAD2 exomes

AF:

0.0514

AC:

12892

AN:

250902

AF XY:

0.0455

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.0435

Gnomad ASJ exome

AF:

0.0392

Gnomad EAS exome

AF:

0.0244

Gnomad FIN exome

AF:

0.0422

Gnomad NFE exome

AF:

0.0432

Gnomad OTH exome

AF:

0.0474

GnomAD4 exome

AF:

0.0464

AC:

67833

AN:

1461102

Hom.:

2528

Cov.:

AF XY:

0.0443

AC XY:

32177

AN XY:

726886

show subpopulations

African (AFR)

AF:

0.264

AC:

8850

AN:

33478

American (AMR)

AF:

0.0500

AC:

2234

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0388

AC:

1015

AN:

26128

East Asian (EAS)

AF:

0.0225

AC:

892

AN:

39694

South Asian (SAS)

AF:

0.00667

AC:

575

AN:

86258

European-Finnish (FIN)

AF:

0.0385

AC:

2031

AN:

52694

Middle Eastern (MID)

AF:

0.0288

AC:

166

AN:

5768

European-Non Finnish (NFE)

AF:

0.0439

AC:

48812

AN:

1111976

Other (OTH)

AF:

0.0540

AC:

3258

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

4632

9265

13897

18530

23162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1964

3928

5892

7856

9820

<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:

0.102

AC:

15606

AN:

152298

Hom.:

1482

Cov.:

AF XY:

0.100

AC XY:

7446

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.248

AC:

10307

AN:

41530

American (AMR)

AF:

0.0800

AC:

1224

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0363

AC:

126

AN:

3472

East Asian (EAS)

AF:

0.0299

AC:

155

AN:

5190

South Asian (SAS)

AF:

0.00931

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0449

AC:

477

AN:

10622

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0438

AC:

2981

AN:

68028

Other (OTH)

AF:

0.0922

AC:

195

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

660

1321

1981

2642

3302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.0601

Hom.:

1667

Bravo

AF:

0.113

Asia WGS

AF:

0.0450

AC:

159

AN:

3478

EpiCase

AF:

0.0384

EpiControl

AF:

0.0407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.3

(source)

DANN

Benign

0.91

PhyloP100

0.88

Mutation Taster

=96/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over