rs1378149

Positions:

• chr4-185932875-T-C

Variant summary

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

The ENST00000284776.11(SORBS2):​c.-338+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 ENST00000284776.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS2	NM_001270771.3	c.-258+23321A>G		intron_variant			NP_001257700.1
SORBS2	NM_001394248.1	c.-173+23321A>G		intron_variant			NP_001381177.1
SORBS2	NM_001394255.1	c.-169+23321A>G		intron_variant			NP_001381184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS2	ENST00000284776.11	c.-338+23321A>G		intron_variant		1		ENSP00000284776
SORBS2	ENST00000469627.1	n.153+23321A>G		intron_variant, non_coding_transcript_variant		1
SORBS2	ENST00000355634.9	c.-258+23321A>G		intron_variant		2		ENSP00000347852	P1

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

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.307

Alfa AF: 0.297 Hom.: 3440

Bravo AF: 0.283

Asia WGS AF: 0.264 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1378149; hg19: chr4-186854029;