10-95454661-T-C

Variant names:

• chr10-95454661-T-C
• rs10450393
• NM_001034954.3:c.-45-13481A>G

Variant summary

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

The NM_001034954.3(SORBS1):​c.-45-13481A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,006 control chromosomes in the GnomAD database, including 16,445 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 0.46 (16445 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	NM_001034954.3	MANE Select	c.-45-13481A>G		intron	N/A	NP_001030126.2
	SORBS1	NM_001384452.1		c.-45-13481A>G		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.-45-13481A>G		intron	N/A	NP_001371377.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	ENST00000371247.7	TSL:5 MANE Select	c.-45-13481A>G		intron	N/A	ENSP00000360293.2
	SORBS1	ENST00000371227.8	TSL:1	c.-45-13481A>G		intron	N/A	ENSP00000360271.3
	SORBS1	ENST00000371249.6	TSL:1	c.-45-13481A>G		intron	N/A	ENSP00000360295.2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69257 AN: 151888 Hom.: 16432 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.456 AC: 69328 AN: 152006 Hom.: 16445 Cov.: 32 AF XY: 0.459 AC XY: 34125 AN XY: 74288

African (AFR) AF: 0.560 AC: 23208 AN: 41478

American (AMR) AF: 0.449 AC: 6864 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1552 AN: 3466

East Asian (EAS) AF: 0.659 AC: 3402 AN: 5166

South Asian (SAS) AF: 0.545 AC: 2626 AN: 4818

European-Finnish (FIN) AF: 0.378 AC: 3981 AN: 10536

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26251 AN: 67944

Other (OTH) AF: 0.455 AC: 961 AN: 2112

Alfa AF: 0.431 Hom.: 2463

Bravo AF: 0.469

Asia WGS AF: 0.573 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10450393; hg19: chr10-97214418;