rs11940126

Variant names:

• chr4-185869755-G-A
• rs11940126
• ENST00000284776.11:c.-338+86441C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-185869755-G-A
• chr4-185869755-G-C

Variant summary

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

The ENST00000284776.11(SORBS2):​c.-338+86441C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 152,264 control chromosomes in the GnomAD database, including 304 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 0.059 (304 hom., cov: 33)
• Consequence: SORBS2 ENST00000284776.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 3 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

ENSG00000296399 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS2	NM_001394248.1	c.-173+86441C>T		intron_variant	Intron 1 of 23		NP_001381177.1
SORBS2	NM_001270771.3	c.-181+24542C>T		intron_variant	Intron 2 of 23		NP_001257700.1
SORBS2	NM_001394255.1	c.-169+86441C>T		intron_variant	Intron 1 of 21		NP_001381184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS2	ENST00000284776.11	c.-338+86441C>T		intron_variant	Intron 1 of 20	1		ENSP00000284776.7
SORBS2	ENST00000469627.1	n.153+86441C>T		intron_variant	Intron 1 of 1	1
SORBS2	ENST00000421420.6	c.-177+86441C>T		intron_variant	Intron 1 of 24	4		ENSP00000393258.2

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8992 AN: 152146 Hom.: 304 Cov.: 33

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0479

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0464

Gnomad OTH AF: 0.0564

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

GnomAD4 genome AF: 0.0591 AC: 9003 AN: 152264 Hom.: 304 Cov.: 33 AF XY: 0.0590 AC XY: 4393 AN XY: 74450

African (AFR) AF: 0.0681 AC: 2830 AN: 41540

American (AMR) AF: 0.0839 AC: 1283 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3470

East Asian (EAS) AF: 0.137 AC: 708 AN: 5184

South Asian (SAS) AF: 0.0485 AC: 234 AN: 4822

European-Finnish (FIN) AF: 0.0432 AC: 458 AN: 10608

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0464 AC: 3155 AN: 68020

Other (OTH) AF: 0.0553 AC: 117 AN: 2116

Alfa AF: 0.0498 Hom.: 361

Bravo AF: 0.0651

Asia WGS AF: 0.0700 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.61
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11940126; hg19: chr4-186790909;