rs7900095

Positions:

• chr10-95359292-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.1956-1489A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,112 control chromosomes in the GnomAD database, including 31,474 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 0.64 (31474 hom., cov: 33)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.1956-1489A>G		intron_variant		ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.1956-1489A>G		intron_variant		5	NM_001034954.3	P3

Frequencies

GnomAD3 genomes AF: 0.638 AC: 97034 AN: 151992 Hom.: 31461 Cov.: 33

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.638 AC: 97078 AN: 152112 Hom.: 31474 Cov.: 33 AF XY: 0.637 AC XY: 47400 AN XY: 74364

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.655

Alfa AF: 0.637 Hom.: 51093

Bravo AF: 0.650

Asia WGS AF: 0.540 AC: 1879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.8
DANN	Benign	0.45

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: rs7900095; hg19: chr10-97119049;