10-95510972-C-T

Variant names:

• chr10-95510972-C-T
• rs12247017
• NM_001034954.3:c.-131-19852G>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.-131-19852G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 152,192 control chromosomes in the GnomAD database, including 693 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 0.087 (693 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0997 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-131-19852G>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.-131-19852G>A		intron_variant	Intron 1 of 32	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.0873 AC: 13279 AN: 152074 Hom.: 691 Cov.: 32

Gnomad AFR AF: 0.0726

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0820

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0857

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

GnomAD4 genome AF: 0.0873 AC: 13290 AN: 152192 Hom.: 693 Cov.: 32 AF XY: 0.0869 AC XY: 6463 AN XY: 74396

African (AFR) AF: 0.0727 AC: 3020 AN: 41526

American (AMR) AF: 0.0819 AC: 1252 AN: 15286

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0139 AC: 67 AN: 4826

European-Finnish (FIN) AF: 0.153 AC: 1620 AN: 10588

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

European-Non Finnish (NFE) AF: 0.102 AC: 6917 AN: 68000

Other (OTH) AF: 0.0848 AC: 179 AN: 2110

Alfa AF: 0.0906 Hom.: 1306

Bravo AF: 0.0820

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	-0.89
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-0.19
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: rs12247017; hg19: chr10-97270729;