chr2-234991527-T-A

Variant names:

• chr2-234991527-T-A
• rs11676855
• NM_014521.3:c.-206-3776T>A

Variant summary

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

The NM_014521.3(SH3BP4):​c.-206-3776T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: SH3BP4 NM_014521.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• Publications: 12 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: 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=-0.91).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP4	NM_014521.3	MANE Select	c.-206-3776T>A		intron	N/A	NP_055336.1	Q9P0V3-1
	SH3BP4	NM_001371302.1		c.-206-3776T>A		intron	N/A	NP_001358231.1	Q9P0V3-1
	SH3BP4	NM_001371303.1		c.-206-3776T>A		intron	N/A	NP_001358232.1	Q9P0V3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP4	ENST00000392011.7	TSL:1 MANE Select	c.-206-3776T>A		intron	N/A	ENSP00000375867.2	Q9P0V3-1
	SH3BP4	ENST00000344528.8	TSL:1	c.-122-3776T>A		intron	N/A	ENSP00000340237.4	Q9P0V3-1
	SH3BP4	ENST00000409212.5	TSL:5	c.-206-3776T>A		intron	N/A	ENSP00000386862.1	Q9P0V3-1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.60
PhyloP100		-0.60

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: rs11676855; hg19: chr2-235900171;