chr13-109778421-G-C

Variant names:

• chr13-109778421-G-C
• rs7997595
• NM_003749.3:c.4012+3621C>G

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+3621C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,262 control chromosomes in the GnomAD database, including 56,533 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 0.86 (56533 hom., cov: 33)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS2	NM_003749.3	c.4012+3621C>G		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+3621C>G		intron_variant	Intron 1 of 1	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130922 AN: 152144 Hom.: 56484 Cov.: 33

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.861 AC: 131029 AN: 152262 Hom.: 56533 Cov.: 33 AF XY: 0.860 AC XY: 64038 AN XY: 74444

African (AFR) AF: 0.906 AC: 37651 AN: 41540

American (AMR) AF: 0.887 AC: 13567 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3020 AN: 3472

East Asian (EAS) AF: 0.753 AC: 3899 AN: 5176

South Asian (SAS) AF: 0.790 AC: 3811 AN: 4822

European-Finnish (FIN) AF: 0.871 AC: 9247 AN: 10612

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 57025 AN: 68022

Other (OTH) AF: 0.850 AC: 1796 AN: 2114

Alfa AF: 0.820 Hom.: 2597

Bravo AF: 0.866

Asia WGS AF: 0.775 AC: 2696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.34
PhyloP100		-0.97
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

Publications

LitVar

Other links and lift over

dbSNP: rs7997595; hg19: chr13-110430768;