chr16-75260313-T-C

Position:

• chr16-75260313-T-C

Variant summary

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

The XR_933740.3(LOC105371344):​n.437-856T>C 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 0.436 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: LOC105371344 XR_933740.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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=-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/exons	MANE	UniProt
LOC105371344	XR_933740.3	n.437-856T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAR1	ENST00000393422.6	c.66+7602A>G		intron_variant		2
BCAR1	ENST00000418647.7	c.150+4038A>G		intron_variant		2
BCAR1	ENST00000420641.7	c.66+6401A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.443

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4261573; hg19: chr16-75294211;