10-95471763-G-T

Variant names:

• chr10-95471763-G-T
• rs11595114
• NM_001034954.3:c.-46+19272C>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.-46+19272C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,980 control chromosomes in the GnomAD database, including 3,459 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 0.20 (3459 hom., cov: 31)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 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.-46+19272C>A		intron	N/A	NP_001030126.2
	SORBS1	NM_001384452.1		c.-46+19272C>A		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.-46+19272C>A		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.-46+19272C>A		intron	N/A	ENSP00000360293.2
	SORBS1	ENST00000371227.8	TSL:1	c.-46+19272C>A		intron	N/A	ENSP00000360271.3
	SORBS1	ENST00000371249.6	TSL:1	c.-46+19272C>A		intron	N/A	ENSP00000360295.2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30456 AN: 151862 Hom.: 3464 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.200 AC: 30452 AN: 151980 Hom.: 3459 Cov.: 31 AF XY: 0.201 AC XY: 14900 AN XY: 74286

African (AFR) AF: 0.106 AC: 4386 AN: 41474

American (AMR) AF: 0.239 AC: 3641 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3466

East Asian (EAS) AF: 0.0215 AC: 111 AN: 5168

South Asian (SAS) AF: 0.301 AC: 1442 AN: 4792

European-Finnish (FIN) AF: 0.208 AC: 2200 AN: 10572

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16945 AN: 67940

Other (OTH) AF: 0.219 AC: 461 AN: 2108

Alfa AF: 0.227 Hom.: 1554

Bravo AF: 0.195

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.83
PhyloP100		-0.23
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: rs11595114; hg19: chr10-97231520;