chr2-226739189-C-A

Position:

• chr2-226739189-C-A

Variant summary

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

The NM_005544.3(IRS1):​c.*22-2939G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 152,292 control chromosomes in the GnomAD database, including 586 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 0.073 (586 hom., cov: 32)
• Consequence: IRS1 NM_005544.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

Genes affected

IRS1 (HGNC:6125): (insulin receptor substrate 1) This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene are associated with type II diabetes and susceptibility to insulin resistance. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRS1	NM_005544.3	c.*22-2939G>T		intron_variant		ENST00000305123.6	NP_005535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRS1	ENST00000305123.6	c.*22-2939G>T		intron_variant		1	NM_005544.3	ENSP00000304895.4

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11055 AN: 152174 Hom.: 586 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0692

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

GnomAD4 genome AF: 0.0726 AC: 11052 AN: 152292 Hom.: 586 Cov.: 32 AF XY: 0.0729 AC XY: 5431 AN XY: 74468

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0384

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0681

Alfa AF: 0.0816 Hom.: 317

Bravo AF: 0.0646

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.73

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: rs17208470; hg19: chr2-227603905;