rs10786211

Positions:

• chr10-95451979-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.-45-10799G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,990 control chromosomes in the GnomAD database, including 14,434 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 0.42 (14434 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.-45-10799G>A		intron_variant		ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.-45-10799G>A		intron_variant		5	NM_001034954.3	P3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63745 AN: 151872 Hom.: 14403 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.420 AC: 63842 AN: 151990 Hom.: 14434 Cov.: 32 AF XY: 0.424 AC XY: 31515 AN XY: 74314

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.396

Alfa AF: 0.379 Hom.: 1423

Bravo AF: 0.433

Asia WGS AF: 0.546 AC: 1893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.9
DANN	Benign	0.42

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: rs10786211; hg19: chr10-97211736;