16-75261741-C-A

Position:

• chr16-75261741-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_933740.3(LOC105371344):​n.555-398C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,200 control chromosomes in the GnomAD database, including 1,794 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 0.14 (1794 hom., cov: 33)
• Consequence: LOC105371344 XR_933740.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

Genes affected

LOC105371344 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105371344	XR_933740.3	n.555-398C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCAR1	ENST00000393422.6	c.66+6174G>T		intron_variant		2		ENSP00000377074
BCAR1	ENST00000418647.7	c.150+2610G>T		intron_variant		2		ENSP00000391669
BCAR1	ENST00000420641.7	c.66+4973G>T		intron_variant		2		ENSP00000392708

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21571 AN: 152080 Hom.: 1792 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.142 AC: 21583 AN: 152200 Hom.: 1794 Cov.: 33 AF XY: 0.142 AC XY: 10543 AN XY: 74412

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0789

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.127

Alfa AF: 0.112 Hom.: 468

Bravo AF: 0.145

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13337397; hg19: chr16-75295639;