10-95545779-C-T

Variant names:

• chr10-95545779-C-T
• rs1536444
• NM_001034954.3:c.-132+15541G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034954.3(SORBS1):​c.-132+15541G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 151,638 control chromosomes in the GnomAD database, including 29,840 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 0.62 (29840 hom., cov: 31)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034954.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	NM_001034954.3	MANE Select	c.-132+15541G>A		intron	N/A	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.-132+15541G>A		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.-132+15541G>A		intron	N/A	NP_001371377.1	A0A3B3IRW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	ENST00000371247.7	TSL:5 MANE Select	c.-132+15541G>A		intron	N/A	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.-132+15541G>A		intron	N/A	ENSP00000360271.3	Q9BX66-11
	SORBS1	ENST00000371249.6	TSL:1	c.-132+15541G>A		intron	N/A	ENSP00000360295.2	Q9BX66-10

Frequencies

GnomAD3 genomes AF: 0.620 AC: 93944 AN: 151524 Hom.: 29831 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.620 AC: 93976 AN: 151638 Hom.: 29840 Cov.: 31 AF XY: 0.620 AC XY: 45884 AN XY: 74064

African (AFR) AF: 0.486 AC: 20111 AN: 41346

American (AMR) AF: 0.634 AC: 9664 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2063 AN: 3468

East Asian (EAS) AF: 0.783 AC: 4019 AN: 5136

South Asian (SAS) AF: 0.490 AC: 2360 AN: 4818

European-Finnish (FIN) AF: 0.738 AC: 7734 AN: 10486

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45863 AN: 67832

Other (OTH) AF: 0.630 AC: 1330 AN: 2110

Alfa AF: 0.648 Hom.: 52021

Bravo AF: 0.612

Asia WGS AF: 0.636 AC: 2207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.51
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1536444; hg19: chr10-97305536;