rs4773088

Variant names:

• chr13-109769537-G-A
• rs4773088
• NM_003749.3:c.4012+12505C>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+12505C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,842 control chromosomes in the GnomAD database, including 7,558 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 0.31 (7558 hom., cov: 32)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003749.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRS2	NM_003749.3	MANE Select	c.4012+12505C>T		intron	N/A	NP_003740.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRS2	ENST00000375856.5	TSL:1 MANE Select	c.4012+12505C>T		intron	N/A	ENSP00000365016.3	Q9Y4H2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47579 AN: 151724 Hom.: 7557 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.313 AC: 47602 AN: 151842 Hom.: 7558 Cov.: 32 AF XY: 0.312 AC XY: 23137 AN XY: 74186

African (AFR) AF: 0.324 AC: 13413 AN: 41388

American (AMR) AF: 0.272 AC: 4150 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1244 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1156 AN: 5154

South Asian (SAS) AF: 0.362 AC: 1741 AN: 4808

European-Finnish (FIN) AF: 0.327 AC: 3440 AN: 10526

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.313 AC: 21256 AN: 67914

Other (OTH) AF: 0.354 AC: 747 AN: 2108

Alfa AF: 0.318 Hom.: 13166

Bravo AF: 0.310

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.032
DANN	Benign	0.29
PhyloP100		-1.4
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: rs4773088; hg19: chr13-110421884;