rs7076888

Positions:

• chr10-95356462-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001034954.3(SORBS1):​c.2128+1169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,550,148 control chromosomes in the GnomAD database, including 241,970 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 0.56 (24413 hom., cov: 31)
  • Exomes 𝑓: 0.56 (217557 hom.)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

Genes affected

SORBS1 (HGNC:14565): (sorbin and SH3 domain containing 1) This gene encodes a CBL-associated protein which functions in the signaling and stimulation of insulin. Mutations in this gene may be associated with human disorders of insulin resistance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.2128+1169G>A		intron_variant		ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.2128+1169G>A		intron_variant		5	NM_001034954.3	ENSP00000360293	P3

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85388 AN: 151854 Hom.: 24389 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.573

GnomAD3 exomes AF: 0.577 AC: 85911 AN: 149016 Hom.: 25496 AF XY: 0.575 AC XY: 46149 AN XY: 80246

Gnomad AFR exome AF: 0.579

Gnomad AMR exome AF: 0.706

Gnomad ASJ exome AF: 0.653

Gnomad EAS exome AF: 0.322

Gnomad SAS exome AF: 0.622

Gnomad FIN exome AF: 0.531

Gnomad NFE exome AF: 0.551

Gnomad OTH exome AF: 0.581

GnomAD4 exome AF: 0.555 AC: 776686 AN: 1398176 Hom.: 217557 Cov.: 102 AF XY: 0.557 AC XY: 384345 AN XY: 689594

Gnomad4 AFR exome AF: 0.582

Gnomad4 AMR exome AF: 0.695

Gnomad4 ASJ exome AF: 0.655

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.618

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.551

Gnomad4 OTH exome AF: 0.556

GnomAD4 genome AF: 0.562 AC: 85457 AN: 151972 Hom.: 24413 Cov.: 31 AF XY: 0.563 AC XY: 41831 AN XY: 74240

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.568

Alfa AF: 0.555 Hom.: 37606

Bravo AF: 0.573

Asia WGS AF: 0.492 AC: 1713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.88

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: rs7076888; hg19: chr10-97116219; COSMIC: COSV53353317; COSMIC: COSV53353317;