10-95469038-C-T

Position:

• chr10-95469038-C-T

Variant summary

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

The NM_001034954.3(SORBS1):​c.-46+21997G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,072 control chromosomes in the GnomAD database, including 4,598 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 0.24 (4598 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-46+21997G>A		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+21997G>A		intron_variant		5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36894 AN: 151954 Hom.: 4600 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.243 AC: 36919 AN: 152072 Hom.: 4598 Cov.: 32 AF XY: 0.242 AC XY: 17960 AN XY: 74364

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.249

Alfa AF: 0.245 Hom.: 4414

Bravo AF: 0.243

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.87

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: rs12414693; hg19: chr10-97228795;