16-75260313-T-C

Variant names:

• chr16-75260313-T-C
• rs4261573
• NM_001170714.3:c.150+4038A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 13 publications found

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]

LOC105371344 (HGNC:):

ACMG classification

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAR1	ENST00000418647.7	c.150+4038A>G		intron_variant	Intron 2 of 7	2		ENSP00000391669.3
BCAR1	ENST00000393422.6	c.66+7602A>G		intron_variant	Intron 1 of 6	2		ENSP00000377074.2
BCAR1	ENST00000420641.7	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.: 33

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.: 33 AF XY: 0.443 AC XY: 32928 AN XY: 74334

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

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
DANN	Benign	0.34
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4261573; hg19: chr16-75294211;