rs6818789

Variant names:

• chr4-185601799-C-T
• rs6818789
• NM_001395207.1:c.3685-7864G>A

Variant summary

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

The NM_001395207.1(SORBS2):​c.3685-7864G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,966 control chromosomes in the GnomAD database, including 7,394 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 0.25 (7394 hom., cov: 32)
• Consequence: SORBS2 NM_001395207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS2	NM_001395207.1	c.3685-7864G>A		intron_variant	Intron 24 of 26	ENST00000695409.1	NP_001382136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS2	ENST00000695409.1	c.3685-7864G>A		intron_variant	Intron 24 of 26		NM_001395207.1	ENSP00000511888.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37621 AN: 151848 Hom.: 7373 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.248 AC: 37686 AN: 151966 Hom.: 7394 Cov.: 32 AF XY: 0.249 AC XY: 18463 AN XY: 74282

African (AFR) AF: 0.546 AC: 22616 AN: 41402

American (AMR) AF: 0.132 AC: 2008 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 166 AN: 3468

East Asian (EAS) AF: 0.319 AC: 1644 AN: 5156

South Asian (SAS) AF: 0.239 AC: 1152 AN: 4814

European-Finnish (FIN) AF: 0.166 AC: 1754 AN: 10566

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7732 AN: 67978

Other (OTH) AF: 0.191 AC: 403 AN: 2108

Alfa AF: 0.143 Hom.: 4092

Bravo AF: 0.258

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		-0.27
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: rs6818789; hg19: chr4-186522953;