10-95524605-C-T

Variant names:

• chr10-95524605-C-T
• rs12776555
• NM_001034954.3:c.-131-33485G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034954.3(SORBS1):​c.-131-33485G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 152,282 control chromosomes in the GnomAD database, including 698 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 0.089 (698 hom., cov: 33)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0998 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-131-33485G>A		intron_variant	Intron 1 of 32	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.-131-33485G>A		intron_variant	Intron 1 of 32	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13478 AN: 152164 Hom.: 696 Cov.: 33

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0840

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

GnomAD4 genome AF: 0.0886 AC: 13487 AN: 152282 Hom.: 698 Cov.: 33 AF XY: 0.0877 AC XY: 6529 AN XY: 74460

African (AFR) AF: 0.0775 AC: 3221 AN: 41572

American (AMR) AF: 0.0817 AC: 1249 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 207 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0139 AC: 67 AN: 4832

European-Finnish (FIN) AF: 0.152 AC: 1614 AN: 10586

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6925 AN: 68016

Other (OTH) AF: 0.0832 AC: 176 AN: 2116

Alfa AF: 0.0946 Hom.: 107

Bravo AF: 0.0837

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.67
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12776555; hg19: chr10-97284362;