16-75233836-G-T

Variant names:

• chr16-75233836-G-T
• rs201219624
• NM_014567.5:c.2100+10C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014567.5(BCAR1):​c.2100+10C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,896 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BCAR1 NM_014567.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641
• Publications: 0 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAR1	NM_014567.5	MANE Select	c.2100+10C>A		intron	N/A	NP_055382.2
	BCAR1	NM_001170714.3		c.2238+10C>A		intron	N/A	NP_001164185.1	P56945-6
	BCAR1	NM_001170715.3		c.2154+10C>A		intron	N/A	NP_001164186.1	P56945-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAR1	ENST00000162330.10	TSL:1 MANE Select	c.2100+10C>A		intron	N/A	ENSP00000162330.5	P56945-1
	BCAR1	ENST00000563038.5	TSL:1	n.1705+10C>A		intron	N/A
	BCAR1	ENST00000418647.7	TSL:2	c.2238+10C>A		intron	N/A	ENSP00000391669.3	P56945-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442896 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 716240

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33184

American (AMR) AF: 0.00 AC: 0 AN: 42262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25636

East Asian (EAS) AF: 0.00 AC: 0 AN: 38930

South Asian (SAS) AF: 0.00 AC: 0 AN: 83518

European-Finnish (FIN) AF: 0.0000197 AC: 1 AN: 50864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103196

Other (OTH) AF: 0.00 AC: 0 AN: 59650

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.77
PhyloP100		-0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs201219624; hg19: chr16-75267734;