2-234991527-T-C

Position:

• chr2-234991527-T-C

Variant summary

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

The ENST00000392011.7(SH3BP4):​c.-206-3776T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,034 control chromosomes in the GnomAD database, including 18,196 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 0.46 (18196 hom., cov: 33)
• Consequence: SH3BP4 ENST00000392011.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599

Genes affected

SH3BP4 (HGNC:10826): (SH3 domain binding protein 4) This gene encodes a protein with 3 Asn-Pro-Phe (NPF) motifs, an SH3 domain, a PXXP motif, a bipartite nuclear targeting signal, and a tyrosine phosphorylation site. This protein is involved in cargo-specific control of clathrin-mediated endocytosis, specifically controlling the internalization of a specific protein receptor. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3BP4	NM_014521.3	c.-206-3776T>C		intron_variant		ENST00000392011.7	NP_055336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3BP4	ENST00000392011.7	c.-206-3776T>C		intron_variant		1	NM_014521.3	ENSP00000375867	P1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70114 AN: 151916 Hom.: 18143 Cov.: 33

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.462 AC: 70224 AN: 152034 Hom.: 18196 Cov.: 33 AF XY: 0.468 AC XY: 34762 AN XY: 74310

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.416

Alfa AF: 0.376 Hom.: 6487

Bravo AF: 0.482

Asia WGS AF: 0.581 AC: 2021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.30
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs11676855; hg19: chr2-235900171;