rs1410059

Positions:

• chr10-95412838-T-C
• chr10-95412838-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.810+1656A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,874 control chromosomes in the GnomAD database, including 20,891 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 0.52 (20891 hom., cov: 31)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.810+1656A>G		intron_variant		ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.810+1656A>G		intron_variant		5	NM_001034954.3	P3

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79074 AN: 151756 Hom.: 20865 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.521 AC: 79143 AN: 151874 Hom.: 20891 Cov.: 31 AF XY: 0.522 AC XY: 38757 AN XY: 74212

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.543

Alfa AF: 0.492 Hom.: 5338

Bravo AF: 0.520

Asia WGS AF: 0.629 AC: 2184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.72

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: rs1410059; hg19: chr10-97172595;