chr4-185742768-T-C

Position:

• chr4-185742768-T-C

Variant summary

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

The NM_001395207.1(SORBS2):​c.-96-8614A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 152,306 control chromosomes in the GnomAD database, including 215 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 0.045 (215 hom., cov: 32)
• Consequence: SORBS2 NM_001395207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS2	NM_001395207.1	c.-96-8614A>G		intron_variant		ENST00000695409.1	NP_001382136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS2	ENST00000695409.1	c.-96-8614A>G		intron_variant			NM_001395207.1	ENSP00000511888

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 6817 AN: 152188 Hom.: 215 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00995

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0447 AC: 6814 AN: 152306 Hom.: 215 Cov.: 32 AF XY: 0.0430 AC XY: 3199 AN XY: 74464

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00954

Gnomad4 FIN AF: 0.0742

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0617 Hom.: 171

Bravo AF: 0.0400

Asia WGS AF: 0.00549 AC: 19 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	0.73
DANN	Benign	0.65

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: rs13144644; hg19: chr4-186663922;