rs4771647

Positions:

• chr13-109774862-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003749.3(IRS2):​c.4012+7180T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,064 control chromosomes in the GnomAD database, including 8,458 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 0.33 (8458 hom., cov: 32)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRS2	NM_003749.3	c.4012+7180T>G		intron_variant		ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5	c.4012+7180T>G		intron_variant		1	NM_003749.3	ENSP00000365016	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50306 AN: 151946 Hom.: 8460 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.331 AC: 50320 AN: 152064 Hom.: 8458 Cov.: 32 AF XY: 0.330 AC XY: 24543 AN XY: 74334

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.365

Alfa AF: 0.339 Hom.: 14132

Bravo AF: 0.324

Asia WGS AF: 0.316 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.41

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: rs4771647; hg19: chr13-110427209;