rs2274490

Positions:

• chr10-95381766-G-A
• chr10-95381766-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001034954.3(SORBS1):​c.1572C>T​(p.Asp524Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,607,052 control chromosomes in the GnomAD database, including 291,029 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 0.57 (25239 hom., cov: 32)
  • Exomes 𝑓: 0.60 (265790 hom.)
• Consequence: SORBS1 NM_001034954.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=3.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.1572C>T	p.Asp524Asp	synonymous_variant	18/33	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.1572C>T	p.Asp524Asp	synonymous_variant	18/33	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86589 AN: 151912 Hom.: 25233 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.610

GnomAD3 exomes AF: 0.628 AC: 156612 AN: 249188 Hom.: 50178 AF XY: 0.627 AC XY: 84433 AN XY: 134708

Gnomad AFR exome AF: 0.449

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.682

Gnomad EAS exome AF: 0.639

Gnomad SAS exome AF: 0.654

Gnomad FIN exome AF: 0.634

Gnomad NFE exome AF: 0.594

Gnomad OTH exome AF: 0.632

GnomAD4 exome AF: 0.601 AC: 874660 AN: 1455022 Hom.: 265790 Cov.: 34 AF XY: 0.603 AC XY: 436340 AN XY: 724160

Gnomad4 AFR exome AF: 0.443

Gnomad4 AMR exome AF: 0.770

Gnomad4 ASJ exome AF: 0.686

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.635

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.598

GnomAD4 genome AF: 0.570 AC: 86631 AN: 152030 Hom.: 25239 Cov.: 32 AF XY: 0.577 AC XY: 42864 AN XY: 74324

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.608

Alfa AF: 0.595 Hom.: 62997

Bravo AF: 0.567

Asia WGS AF: 0.631 AC: 2197 AN: 3478

EpiCase AF: 0.594

EpiControl AF: 0.601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.8
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2274490; hg19: chr10-97141523; COSMIC: COSV53354801; COSMIC: COSV53354801;