rs13150700

Variant names:

• chr4-185688969-T-C
• rs13150700
• NM_001395207.1:c.10+1593A>G

Variant summary

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

The NM_001395207.1(SORBS2):​c.10+1593A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,034 control chromosomes in the GnomAD database, including 4,010 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 0.21 (4010 hom., cov: 32)
• Consequence: SORBS2 NM_001395207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 2 publications found

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]

SORBS2 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395207.1. 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
	SORBS2	NM_001395207.1	MANE Select	c.10+1593A>G		intron	N/A	NP_001382136.1	A0A8Q3WKK4
	SORBS2	NM_001394245.1		c.-32-4123A>G		intron	N/A	NP_001381174.1
	SORBS2	NM_001394246.1		c.-32-4123A>G		intron	N/A	NP_001381175.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS2	ENST00000695409.1	MANE Select	c.10+1593A>G		intron	N/A	ENSP00000511888.1	A0A8Q3WKK4
	SORBS2	ENST00000284776.11	TSL:1	c.-197-10147A>G		intron	N/A	ENSP00000284776.7	O94875-1
	SORBS2	ENST00000437304.6	TSL:1	c.-233-10147A>G		intron	N/A	ENSP00000396008.2	O94875-10

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31911 AN: 151916 Hom.: 4006 Cov.: 32

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.210 AC: 31935 AN: 152034 Hom.: 4010 Cov.: 32 AF XY: 0.212 AC XY: 15773 AN XY: 74292

African (AFR) AF: 0.0925 AC: 3838 AN: 41510

American (AMR) AF: 0.154 AC: 2351 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3472

East Asian (EAS) AF: 0.240 AC: 1242 AN: 5168

South Asian (SAS) AF: 0.199 AC: 960 AN: 4814

European-Finnish (FIN) AF: 0.360 AC: 3798 AN: 10550

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18563 AN: 67924

Other (OTH) AF: 0.182 AC: 384 AN: 2110

Alfa AF: 0.240 Hom.: 14879

Bravo AF: 0.186

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-0.39
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: rs13150700; hg19: chr4-186610123;