rs533480

Positions:

• chr10-95472448-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034954.3(SORBS1):​c.-46+18587C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,048 control chromosomes in the GnomAD database, including 8,398 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 0.33 (8398 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-46+18587C>T		intron_variant		ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.-46+18587C>T		intron_variant		5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49562 AN: 151930 Hom.: 8385 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.326 AC: 49621 AN: 152048 Hom.: 8398 Cov.: 32 AF XY: 0.326 AC XY: 24218 AN XY: 74338

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.315

Alfa AF: 0.308 Hom.: 4120

Bravo AF: 0.324

Asia WGS AF: 0.338 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.34

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: rs533480; hg19: chr10-97232205;