rs11618950

Variant names:

• chr13-109781963-G-A
• rs11618950
• NM_003749.3:c.4012+79C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-109781963-G-A
• chr13-109781963-G-T

Variant summary

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

The NM_003749.3(IRS2):​c.4012+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,508,380 control chromosomes in the GnomAD database, including 25,490 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 (4408 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21082 hom.)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS2	NM_003749.3	c.4012+79C>T		intron_variant	Intron 1 of 1	ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5	c.4012+79C>T		intron_variant	Intron 1 of 1	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33355 AN: 152026 Hom.: 4401 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0207

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.170 AC: 230565 AN: 1356236 Hom.: 21082 AF XY: 0.170 AC XY: 114490 AN XY: 673144

African (AFR) AF: 0.380 AC: 12055 AN: 31748

American (AMR) AF: 0.133 AC: 4922 AN: 37024

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4236 AN: 24880

East Asian (EAS) AF: 0.0385 AC: 1463 AN: 37998

South Asian (SAS) AF: 0.158 AC: 12642 AN: 80198

European-Finnish (FIN) AF: 0.166 AC: 7418 AN: 44716

Middle Eastern (MID) AF: 0.113 AC: 610 AN: 5408

European-Non Finnish (NFE) AF: 0.171 AC: 177783 AN: 1037424

Other (OTH) AF: 0.166 AC: 9436 AN: 56840

GnomAD4 genome AF: 0.219 AC: 33390 AN: 152144 Hom.: 4408 Cov.: 33 AF XY: 0.215 AC XY: 15981 AN XY: 74394

African (AFR) AF: 0.369 AC: 15305 AN: 41476

American (AMR) AF: 0.165 AC: 2523 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 670 AN: 3472

East Asian (EAS) AF: 0.0206 AC: 106 AN: 5156

South Asian (SAS) AF: 0.149 AC: 718 AN: 4828

European-Finnish (FIN) AF: 0.166 AC: 1760 AN: 10602

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

European-Non Finnish (NFE) AF: 0.173 AC: 11780 AN: 67982

Other (OTH) AF: 0.179 AC: 379 AN: 2116

Alfa AF: 0.184 Hom.: 3620

Bravo AF: 0.225

Asia WGS AF: 0.103 AC: 360 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	0.56
DANN	Benign	0.49
PhyloP100		-0.88
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: rs11618950; hg19: chr13-110434310;