rs2274491

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.76+269A>T		intron_variant		ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.76+269A>T		intron_variant		5	NM_001034954.3	P3

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

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.756

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

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: rs2274491; hg19: chr10-97196978;