rs726466

Variant names:

• chr4-185624902-C-G
• rs726466
• NM_001395207.1:c.1523-408G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-185624902-C-G
• chr4-185624902-C-T

Variant summary

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

The NM_001395207.1(SORBS2):​c.1523-408G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,102 control chromosomes in the GnomAD database, including 8,408 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 0.31 (8408 hom., cov: 33)
• Consequence: SORBS2 NM_001395207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS2	NM_001395207.1	c.1523-408G>C		intron_variant	Intron 18 of 26	ENST00000695409.1	NP_001382136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS2	ENST00000695409.1	c.1523-408G>C		intron_variant	Intron 18 of 26		NM_001395207.1	ENSP00000511888.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47627 AN: 151984 Hom.: 8400 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.313 AC: 47644 AN: 152102 Hom.: 8408 Cov.: 33 AF XY: 0.313 AC XY: 23240 AN XY: 74338

African (AFR) AF: 0.150 AC: 6232 AN: 41502

American (AMR) AF: 0.288 AC: 4403 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1508 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1376 AN: 5170

South Asian (SAS) AF: 0.524 AC: 2527 AN: 4824

European-Finnish (FIN) AF: 0.339 AC: 3576 AN: 10546

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26899 AN: 67988

Other (OTH) AF: 0.321 AC: 677 AN: 2112

Alfa AF: 0.229 Hom.: 617

Bravo AF: 0.295

Asia WGS AF: 0.399 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.44
PhyloP100		-0.038
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: rs726466; hg19: chr4-186546056;