rs11188352

Variant names:

• chr10-95541247-T-G
• rs11188352
• NM_001034954.3:c.-132+20073A>C

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+20073A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 151,988 control chromosomes in the GnomAD database, including 1,113 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 0.086 (1113 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-132+20073A>C		intron_variant	Intron 1 of 32	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.-132+20073A>C		intron_variant	Intron 1 of 32	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13028 AN: 151870 Hom.: 1112 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.0492

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0751

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

GnomAD4 genome AF: 0.0859 AC: 13050 AN: 151988 Hom.: 1113 Cov.: 32 AF XY: 0.0836 AC XY: 6214 AN XY: 74298

African (AFR) AF: 0.222 AC: 9200 AN: 41372

American (AMR) AF: 0.0447 AC: 684 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3470

East Asian (EAS) AF: 0.0496 AC: 256 AN: 5166

South Asian (SAS) AF: 0.0722 AC: 347 AN: 4806

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10614

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2051 AN: 67954

Other (OTH) AF: 0.0753 AC: 159 AN: 2112

Alfa AF: 0.0434 Hom.: 307

Bravo AF: 0.0941

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.79
PhyloP100		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11188352; hg19: chr10-97301004;