rs2274491

Variant names:

• chr10-95437221-T-A
• rs2274491
• NM_001034954.3:c.76+269A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-95437221-T-A
• chr10-95437221-T-G

Variant summary

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

The NM_001034954.3(SORBS1):​c.76+269A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,164 control chromosomes in the GnomAD database, including 43,084 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 0.75 (43084 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.76+269A>T		intron_variant	Intron 4 of 32	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.76+269A>T		intron_variant	Intron 4 of 32	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113997 AN: 152046 Hom.: 43042 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.750 AC: 114095 AN: 152164 Hom.: 43084 Cov.: 32 AF XY: 0.751 AC XY: 55857 AN XY: 74398

African (AFR) AF: 0.830 AC: 34426 AN: 41502

American (AMR) AF: 0.773 AC: 11823 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2741 AN: 3472

East Asian (EAS) AF: 0.697 AC: 3606 AN: 5176

South Asian (SAS) AF: 0.863 AC: 4162 AN: 4820

European-Finnish (FIN) AF: 0.653 AC: 6911 AN: 10580

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47913 AN: 67998

Other (OTH) AF: 0.756 AC: 1599 AN: 2114

Alfa AF: 0.614 Hom.: 1615

Bravo AF: 0.762

Asia WGS AF: 0.760 AC: 2641 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	0.050
DANN	Benign	0.50
PhyloP100		-0.66
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: rs2274491; hg19: chr10-97196978;