rs4376189

chr4-185691521-G-Achr4-185691521-G-Cchr4-185691521-G-T

Variant summary

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

The NM_001395207.1(SORBS2):c.-40-910C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 152,250 control chromosomes in the GnomAD database, including 64,639 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 0.92 (64639 hom., cov: 31)
• Consequence: SORBS2 NM_001395207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718

Genes affected

SORBS2 (HGNC:24098): (sorbin and SH3 domain containing 2) Arg and c-Abl represent the mammalian members of the Abelson family of non-receptor protein-tyrosine kinases. They interact with the Arg/Abl binding proteins via the SH3 domains present in the carboxy end of the latter group of proteins. This gene encodes the sorbin and SH3 domain containing 2 protein. It has three C-terminal SH3 domains and an N-terminal sorbin homology (SoHo) domain that interacts with lipid raft proteins. The subcellular localization of this protein in epithelial and cardiac muscle cells suggests that it functions as an adapter protein to assemble signaling complexes in stress fibers, and that it is a potential link between Abl family kinases and the actin cytoskeleton. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS2	NM_001395207.1	c.-40-910C>T		intron_variant		ENST00000695409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS2	ENST00000695409.1	c.-40-910C>T		intron_variant			NM_001395207.1

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140173 AN: 152132 Hom.: 64576 Cov.: 31

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.921 AC: 140295 AN: 152250 Hom.: 64639 Cov.: 31 AF XY: 0.921 AC XY: 68588 AN XY: 74438

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.937

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.907

Gnomad4 NFE AF: 0.909

Gnomad4 OTH AF: 0.911

Alfa AF: 0.910 Hom.: 80710

Bravo AF: 0.925

Asia WGS AF: 0.900 AC: 3131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.043
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: rs4376189; hg19: chr4-186612675;