rs12240292

Positions:

• chr10-95513309-C-T

Variant summary

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

The NM_001034954.3(SORBS1):​c.-131-22189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 92,416 control chromosomes in the GnomAD database, including 681 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 0.14 (681 hom., cov: 31)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.668

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.-131-22189G>A		intron_variant		ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.-131-22189G>A		intron_variant		5	NM_001034954.3	P3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 13218 AN: 92312 Hom.: 679 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0302

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.000470

Gnomad SAS AF: 0.0328

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.0545

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.143 AC: 13230 AN: 92416 Hom.: 681 Cov.: 31 AF XY: 0.145 AC XY: 6432 AN XY: 44266

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0813

Gnomad4 EAS AF: 0.000470

Gnomad4 SAS AF: 0.0323

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0917 Hom.: 102

Bravo AF: 0.0819

Asia WGS AF: 0.0130 AC: 46 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.70

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: rs12240292; hg19: chr10-97273066;