Genetic Variant NM_001170714.3:c.150+4038A>G (chr16-75260313-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001170714.3(BCAR1):c.150+4038A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,078 control chromosomes in the GnomAD database, including 15,893 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 0.44 ( 15893 hom., cov: 33)

Consequence

BCAR1
NM_001170714.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.11

Publications

13 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:

LOC105371344 (HGNC:):

LOC105371344 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=-1.04).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
BCAR1	NM_001170714.3 link	c.150+4038A>G	intron_variant	Intron 2 of 7	NP_001164185.1
BCAR1	NM_001170715.3 link	c.66+7602A>G	intron_variant	Intron 1 of 6	NP_001164186.1
BCAR1	NM_001170716.3 link	c.66+6401A>G	intron_variant	Intron 1 of 6	NP_001164187.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
BCAR1	ENST00000418647.7 link	c.150+4038A>G	intron_variant	Intron 2 of 7	2	ENSP00000391669.3
BCAR1	ENST00000393422.6 link	c.66+7602A>G	intron_variant	Intron 1 of 6	2	ENSP00000377074.2
BCAR1	ENST00000420641.7 link	c.66+6401A>G	intron_variant	Intron 1 of 6	2	ENSP00000392708.3

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

66230

AN:

151960

Hom.:

15867

Cov.:

show subpopulations

Gnomad AFR

AF:

0.574

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.815

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.436

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

GnomAD4 genome

AF:

0.436

AC:

66309

AN:

152078

Hom.:

15893

Cov.:

AF XY:

0.443

AC XY:

32928

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.574

AC:

23798

AN:

41478

American (AMR)

AF:

0.428

AC:

6538

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1521

AN:

3468

East Asian (EAS)

AF:

0.815

AC:

4222

AN:

5182

South Asian (SAS)

AF:

0.600

AC:

2890

AN:

4818

European-Finnish (FIN)

AF:

0.423

AC:

4464

AN:

10564

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.317

AC:

21540

AN:

67980

Other (OTH)

AF:

0.443

AC:

933

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1812

3624

5435

7247

9059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<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:

0.381

Hom.:

2083

Bravo

AF:

0.443

Asia WGS

AF:

0.732

AC:

2544

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.018

(source)

DANN

Benign

0.34

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over