rs1378149

Variant names:

• chr4-185932875-T-C
• rs1378149
• ENST00000284776.11:c.-338+23321A>G

Variant summary

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

The NM_001394248.1(SORBS2):​c.-173+23321A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,184 control chromosomes in the GnomAD database, including 6,639 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 0.29 (6639 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SORBS2 NM_001394248.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394248.1. 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_001394248.1		c.-173+23321A>G		intron	N/A	NP_001381177.1
	SORBS2	NM_001270771.3		c.-258+23321A>G		intron	N/A	NP_001257700.1	O94875-11
	SORBS2	NM_001394255.1		c.-169+23321A>G		intron	N/A	NP_001381184.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS2	ENST00000284776.11	TSL:1	c.-338+23321A>G		intron	N/A	ENSP00000284776.7	O94875-1
	SORBS2	ENST00000469627.1	TSL:1	n.153+23321A>G		intron	N/A
	SORBS2	ENST00000421420.6	TSL:4	c.-177+23321A>G		intron	N/A	ENSP00000393258.2	C9JWC3

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44400 AN: 152066 Hom.: 6639 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.292 AC: 44415 AN: 152184 Hom.: 6639 Cov.: 33 AF XY: 0.293 AC XY: 21801 AN XY: 74372

African (AFR) AF: 0.262 AC: 10891 AN: 41534

American (AMR) AF: 0.282 AC: 4317 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 971 AN: 3466

East Asian (EAS) AF: 0.197 AC: 1022 AN: 5178

South Asian (SAS) AF: 0.338 AC: 1634 AN: 4828

European-Finnish (FIN) AF: 0.366 AC: 3867 AN: 10574

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20624 AN: 67990

Other (OTH) AF: 0.307 AC: 648 AN: 2112

Alfa AF: 0.297 Hom.: 3826

Bravo AF: 0.283

Asia WGS AF: 0.264 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.57
PhyloP100		0.16
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: rs1378149; hg19: chr4-186854029;