rs7981170

Variant names:

• chr13-109779227-C-T
• rs7981170
• NM_003749.3:c.4012+2815G>A

Variant summary

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

The ENST00000375856.5(IRS2):​c.4012+2815G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,152 control chromosomes in the GnomAD database, including 4,432 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 0.22 (4432 hom., cov: 33)
• Consequence: IRS2 ENST00000375856.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 1 publications found

Genes affected

IRS2 (HGNC:6126): (insulin receptor substrate 2) This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an interleukin 4 receptor-associated kinase in response to IL4 treatment. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375856.5. 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
	IRS2	NM_003749.3	MANE Select	c.4012+2815G>A		intron	N/A	NP_003740.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRS2	ENST00000375856.5	TSL:1 MANE Select	c.4012+2815G>A		intron	N/A	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32799 AN: 152034 Hom.: 4424 Cov.: 33

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0304

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.216 AC: 32840 AN: 152152 Hom.: 4432 Cov.: 33 AF XY: 0.212 AC XY: 15746 AN XY: 74382

African (AFR) AF: 0.386 AC: 15985 AN: 41460

American (AMR) AF: 0.175 AC: 2682 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3470

East Asian (EAS) AF: 0.0303 AC: 157 AN: 5184

South Asian (SAS) AF: 0.127 AC: 613 AN: 4830

European-Finnish (FIN) AF: 0.151 AC: 1597 AN: 10598

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10623 AN: 68004

Other (OTH) AF: 0.181 AC: 381 AN: 2110

Alfa AF: 0.183 Hom.: 7033

Bravo AF: 0.224

Asia WGS AF: 0.104 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.1
DANN	Benign	0.50
PhyloP100		0.16
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: rs7981170; hg19: chr13-110431574;