rs10882617

Positions:

• chr10-95555931-G-C

Variant summary

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

The NM_001034954.3(SORBS1):​c.-132+5389C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,184 control chromosomes in the GnomAD database, including 2,164 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 0.16 (2164 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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 -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 = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-132+5389C>G		intron_variant		ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.-132+5389C>G		intron_variant		5	NM_001034954.3	ENSP00000360293	P3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24687 AN: 152066 Hom.: 2160 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.162 AC: 24710 AN: 152184 Hom.: 2164 Cov.: 32 AF XY: 0.165 AC XY: 12253 AN XY: 74404

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.155

Alfa AF: 0.159 Hom.: 251

Bravo AF: 0.163

Asia WGS AF: 0.204 AC: 708 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	2.1
DANN	Benign	0.62

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: rs10882617; hg19: chr10-97315688;