rs7079293

chr10-95359836-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.1956-2033A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,062 control chromosomes in the GnomAD database, including 31,137 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 (31137 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.1956-2033A>G		intron_variant		ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.1956-2033A>G		intron_variant		5	NM_001034954.3	P3

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96511 AN: 151944 Hom.: 31123 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.635 AC: 96563 AN: 152062 Hom.: 31137 Cov.: 32 AF XY: 0.634 AC XY: 47157 AN XY: 74340

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.652

Alfa AF: 0.639 Hom.: 14180

Bravo AF: 0.646

Asia WGS AF: 0.540 AC: 1880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.60
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: rs7079293; hg19: chr10-97119593;