rs12773574

chr10-95414468-T-Cchr10-95414468-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+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 1,518,490 control chromosomes in the GnomAD database, including 1,907 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 0.039 (165 hom., cov: 31)
  • Exomes 𝑓: 0.047 (1742 hom.)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.810+26A>G		intron_variant		ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.810+26A>G		intron_variant		5	NM_001034954.3	P3

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5941 AN: 151704 Hom.: 165 Cov.: 31

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0536

Gnomad OTH AF: 0.0537

GnomAD3 exomes AF: 0.0407 AC: 7168 AN: 175986 Hom.: 200 AF XY: 0.0425 AC XY: 3949 AN XY: 92824

Gnomad AFR exome AF: 0.00876

Gnomad AMR exome AF: 0.0390

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.000252

Gnomad SAS exome AF: 0.0271

Gnomad FIN exome AF: 0.0423

Gnomad NFE exome AF: 0.0531

Gnomad OTH exome AF: 0.0493

GnomAD4 exome AF: 0.0474 AC: 64735 AN: 1366668 Hom.: 1742 Cov.: 31 AF XY: 0.0475 AC XY: 31822 AN XY: 669678

Gnomad4 AFR exome AF: 0.00961

Gnomad4 AMR exome AF: 0.0407

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.000283

Gnomad4 SAS exome AF: 0.0277

Gnomad4 FIN exome AF: 0.0405

Gnomad4 NFE exome AF: 0.0508

Gnomad4 OTH exome AF: 0.0455

GnomAD4 genome AF: 0.0391 AC: 5937 AN: 151822 Hom.: 165 Cov.: 31 AF XY: 0.0386 AC XY: 2864 AN XY: 74180

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0483

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0273

Gnomad4 FIN AF: 0.0395

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.0527

Alfa AF: 0.0480 Hom.: 28

Bravo AF: 0.0393

Asia WGS AF: 0.0180 AC: 64 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	0.32
Dann	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12773574; hg19: chr10-97174225;