rs3193970

Positions:

• chr10-95312251-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.*2808A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,448 control chromosomes in the GnomAD database, including 11,577 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 0.39 (11546 hom., cov: 32)
  • Exomes 𝑓: 0.37 (31 hom.)
• Consequence: SORBS1 NM_001034954.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.*2808A>G		3_prime_UTR_variant	33/33	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247	c.*2808A>G		3_prime_UTR_variant	33/33	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58601 AN: 151898 Hom.: 11525 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.370 AC: 160 AN: 432 Hom.: 31 Cov.: 0 AF XY: 0.396 AC XY: 103 AN XY: 260

Gnomad4 FIN exome AF: 0.371

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.386 AC: 58667 AN: 152016 Hom.: 11546 Cov.: 32 AF XY: 0.379 AC XY: 28190 AN XY: 74288

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.352

Alfa AF: 0.408 Hom.: 6757

Bravo AF: 0.376

Asia WGS AF: 0.351 AC: 1220 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.89

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: rs3193970; hg19: chr10-97072008; COSMIC: COSV53365027; COSMIC: COSV53365027;