chr10-95364128-G-A

Position:

• chr10-95364128-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.1955+3522C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,962 control chromosomes in the GnomAD database, including 27,955 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 0.60 (27955 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.67

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.1955+3522C>T		intron_variant		ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.1955+3522C>T		intron_variant		5	NM_001034954.3	P3

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91353 AN: 151844 Hom.: 27937 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.601 AC: 91403 AN: 151962 Hom.: 27955 Cov.: 32 AF XY: 0.603 AC XY: 44824 AN XY: 74286

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.600

Alfa AF: 0.587 Hom.: 34708

Bravo AF: 0.611

Asia WGS AF: 0.507 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.022
DANN	Benign	0.31

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: rs955760; hg19: chr10-97123885;