rs1862737

Variant names:

• chr16-75248066-A-C
• rs1862737
• NM_014567.5:c.12+3405T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-75248066-A-C
• chr16-75248066-A-G
• chr16-75248066-A-T

Variant summary

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

The NM_014567.5(BCAR1):​c.12+3405T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,563,056 control chromosomes in the GnomAD database, including 226,531 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 0.49 (19303 hom., cov: 32)
  • Exomes 𝑓: 0.54 (207228 hom.)
• Consequence: BCAR1 NM_014567.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 22 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]

ENSG00000280152 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014567.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAR1	NM_014567.5	MANE Select	c.12+3405T>G		intron	N/A	NP_055382.2
	BCAR1	NM_001170719.3		c.-7T>G		5_prime_UTR	Exon 1 of 7	NP_001164190.1
	BCAR1	NM_001170714.3		c.151-4976T>G		intron	N/A	NP_001164185.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAR1	ENST00000162330.10	TSL:1 MANE Select	c.12+3405T>G		intron	N/A	ENSP00000162330.5
	ENSG00000280152	ENST00000624205.1	TSL:6	n.2012T>G		non_coding_transcript_exon	Exon 1 of 1
	BCAR1	ENST00000542031.6	TSL:2	c.-7T>G		5_prime_UTR	Exon 1 of 7	ENSP00000440415.2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74944 AN: 151836 Hom.: 19292 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.529

GnomAD2 exomes AF: 0.560 AC: 130694 AN: 233566 AF XY: 0.554

Gnomad AFR exome AF: 0.340

Gnomad AMR exome AF: 0.755

Gnomad ASJ exome AF: 0.478

Gnomad EAS exome AF: 0.583

Gnomad FIN exome AF: 0.585

Gnomad NFE exome AF: 0.535

Gnomad OTH exome AF: 0.554

GnomAD4 exome AF: 0.539 AC: 760115 AN: 1411102 Hom.: 207228 Cov.: 27 AF XY: 0.538 AC XY: 378961 AN XY: 704638

African (AFR) AF: 0.344 AC: 11200 AN: 32556

American (AMR) AF: 0.737 AC: 32893 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 12501 AN: 25922

East Asian (EAS) AF: 0.590 AC: 23298 AN: 39506

South Asian (SAS) AF: 0.541 AC: 46178 AN: 85394

European-Finnish (FIN) AF: 0.586 AC: 22834 AN: 38966

Middle Eastern (MID) AF: 0.491 AC: 2792 AN: 5692

European-Non Finnish (NFE) AF: 0.535 AC: 577341 AN: 1079408

Other (OTH) AF: 0.527 AC: 31078 AN: 58998

GnomAD4 genome AF: 0.494 AC: 74995 AN: 151954 Hom.: 19303 Cov.: 32 AF XY: 0.500 AC XY: 37106 AN XY: 74284

African (AFR) AF: 0.344 AC: 14252 AN: 41408

American (AMR) AF: 0.632 AC: 9663 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3468

East Asian (EAS) AF: 0.588 AC: 3029 AN: 5152

South Asian (SAS) AF: 0.535 AC: 2570 AN: 4804

European-Finnish (FIN) AF: 0.593 AC: 6270 AN: 10580

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35926 AN: 67942

Other (OTH) AF: 0.528 AC: 1116 AN: 2114

Alfa AF: 0.518 Hom.: 82559

Bravo AF: 0.490

Asia WGS AF: 0.585 AC: 2036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.70
DANN	Benign	0.55
PhyloP100		-0.45
PromoterAI		0.093	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1862737; hg19: chr16-75281964; COSMIC: COSV50785003;