NM_003749.3:c.4013-10749G>A

Variant names:

• chr13-109767057-C-T
• rs9559646
• NM_003749.3:c.4013-10749G>A

Variant summary

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

The NM_003749.3(IRS2):​c.4013-10749G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,084 control chromosomes in the GnomAD database, including 15,315 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 0.43 (15315 hom., cov: 33)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS2	NM_003749.3	c.4013-10749G>A		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.4013-10749G>A		intron_variant	Intron 1 of 1	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65362 AN: 151966 Hom.: 15323 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.430 AC: 65355 AN: 152084 Hom.: 15315 Cov.: 33 AF XY: 0.431 AC XY: 32035 AN XY: 74338

African (AFR) AF: 0.244 AC: 10130 AN: 41496

American (AMR) AF: 0.408 AC: 6235 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2070 AN: 3468

East Asian (EAS) AF: 0.276 AC: 1426 AN: 5168

South Asian (SAS) AF: 0.551 AC: 2655 AN: 4820

European-Finnish (FIN) AF: 0.535 AC: 5653 AN: 10570

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35522 AN: 67968

Other (OTH) AF: 0.461 AC: 972 AN: 2110

Alfa AF: 0.478 Hom.: 40937

Bravo AF: 0.410

Asia WGS AF: 0.402 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.47
PhyloP100		-0.90
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: rs9559646; hg19: chr13-110419404;