10-95524324-C-T

Position:

• chr10-95524324-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034954.3(SORBS1):​c.-131-33204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,086 control chromosomes in the GnomAD database, including 30,092 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 0.63 (30092 hom., cov: 33)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.-131-33204G>A		intron_variant		ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.-131-33204G>A		intron_variant		5	NM_001034954.3	P3

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95412 AN: 151968 Hom.: 30066 Cov.: 33

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.628 AC: 95477 AN: 152086 Hom.: 30092 Cov.: 33 AF XY: 0.635 AC XY: 47226 AN XY: 74350

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.592

Alfa AF: 0.599 Hom.: 55444

Bravo AF: 0.622

Asia WGS AF: 0.654 AC: 2271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.3
DANN	Benign	0.82

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: rs1326934; hg19: chr10-97284081;