NM_014521.3:c.2479-313T>C

Variant names:

• chr2-235052249-T-C
• rs10174126
• NM_014521.3:c.2479-313T>C

Variant summary

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

The NM_014521.3(SH3BP4):​c.2479-313T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,944 control chromosomes in the GnomAD database, including 23,989 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 0.55 (23989 hom., cov: 31)
• Consequence: SH3BP4 NM_014521.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 5 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014521.3. 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
	SH3BP4	NM_014521.3	MANE Select	c.2479-313T>C		intron	N/A	NP_055336.1
	SH3BP4	NM_001371302.1		c.2479-313T>C		intron	N/A	NP_001358231.1
	SH3BP4	NM_001371303.1		c.2479-313T>C		intron	N/A	NP_001358232.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP4	ENST00000392011.7	TSL:1 MANE Select	c.2479-313T>C		intron	N/A	ENSP00000375867.2
	SH3BP4	ENST00000344528.8	TSL:1	c.2479-313T>C		intron	N/A	ENSP00000340237.4
	SH3BP4	ENST00000409212.5	TSL:5	c.2479-313T>C		intron	N/A	ENSP00000386862.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84231 AN: 151826 Hom.: 23965 Cov.: 31

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.555 AC: 84308 AN: 151944 Hom.: 23989 Cov.: 31 AF XY: 0.554 AC XY: 41140 AN XY: 74230

African (AFR) AF: 0.662 AC: 27432 AN: 41462

American (AMR) AF: 0.485 AC: 7410 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2402 AN: 3468

East Asian (EAS) AF: 0.678 AC: 3476 AN: 5130

South Asian (SAS) AF: 0.643 AC: 3078 AN: 4784

European-Finnish (FIN) AF: 0.406 AC: 4288 AN: 10550

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34305 AN: 67966

Other (OTH) AF: 0.566 AC: 1196 AN: 2112

Alfa AF: 0.527 Hom.: 68388

Bravo AF: 0.563

Asia WGS AF: 0.667 AC: 2319 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	3.0
DANN	Benign	0.80
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs10174126; hg19: chr2-235960893;