chr10-95362484-T-C

Position:

• chr10-95362484-T-C

Variant summary

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

The NM_001034954.3(SORBS1):​c.1956-4681A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,946 control chromosomes in the GnomAD database, including 32,160 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 0.65 (32160 hom., cov: 31)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

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]

SORBS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.1956-4681A>G		intron_variant		ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.1956-4681A>G		intron_variant		5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98152 AN: 151828 Hom.: 32147 Cov.: 31

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.646 AC: 98194 AN: 151946 Hom.: 32160 Cov.: 31 AF XY: 0.648 AC XY: 48082 AN XY: 74256

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.661

Alfa AF: 0.651 Hom.: 5452

Bravo AF: 0.654

Asia WGS AF: 0.549 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.51

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: rs4918918; hg19: chr10-97122241;