rs498671

Variant names:

• chr10-95470942-T-C
• rs498671
• NM_001034954.3:c.-46+20093A>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.-46+20093A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,696 control chromosomes in the GnomAD database, including 3,563 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 (3563 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-46+20093A>G		intron_variant	Intron 2 of 32	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.-46+20093A>G		intron_variant	Intron 2 of 32	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29678 AN: 151578 Hom.: 3565 Cov.: 32

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0324

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.196 AC: 29667 AN: 151696 Hom.: 3563 Cov.: 32 AF XY: 0.195 AC XY: 14486 AN XY: 74140

African (AFR) AF: 0.0806 AC: 3333 AN: 41344

American (AMR) AF: 0.190 AC: 2897 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3468

East Asian (EAS) AF: 0.0325 AC: 167 AN: 5138

South Asian (SAS) AF: 0.0946 AC: 455 AN: 4812

European-Finnish (FIN) AF: 0.310 AC: 3260 AN: 10500

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18086 AN: 67886

Other (OTH) AF: 0.193 AC: 408 AN: 2110

Alfa AF: 0.225 Hom.: 510

Bravo AF: 0.184

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.61
PhyloP100		-0.28
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: rs498671; hg19: chr10-97230699;