rs11188352

chr10-95541247-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SORBS1	NM_001034954.3	c.-132+20073A>C		intron_variant		ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7	c.-132+20073A>C		intron_variant		5	NM_001034954.3	P3

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

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0447

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.0496

Gnomad4 SAS AF: 0.0722

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.0753

Alfa AF: 0.0399 Hom.: 206

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11188352; hg19: chr10-97301004;