rs12415681

chr10-95473328-T-C

Variant summary

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

The NM_001034954.3(SORBS1):c.-46+17707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,062 control chromosomes in the GnomAD database, including 3,552 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 0.20 (3552 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.-46+17707A>G		intron_variant		ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.-46+17707A>G		intron_variant		5	NM_001034954.3	P3

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30914 AN: 151944 Hom.: 3557 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.203 AC: 30910 AN: 152062 Hom.: 3552 Cov.: 32 AF XY: 0.204 AC XY: 15153 AN XY: 74320

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.221

Alfa AF: 0.220 Hom.: 479

Bravo AF: 0.197

Asia WGS AF: 0.161 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.6
Dann	Benign	0.74

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: rs12415681; hg19: chr10-97233085;