2-226733125-T-C

Position:

• chr2-226733125-T-C

Variant summary

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

The NM_005544.3(IRS1):​c.*3147A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 152,306 control chromosomes in the GnomAD database, including 429 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 0.061 (429 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IRS1 NM_005544.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRS1	NM_005544.3	c.*3147A>G		3_prime_UTR_variant	2/2	ENST00000305123.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRS1	ENST00000305123.6	c.*3147A>G		3_prime_UTR_variant	2/2	1	NM_005544.3	P1

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9324 AN: 152190 Hom.: 430 Cov.: 32

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0881

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.0602

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0613 AC: 9332 AN: 152306 Hom.: 429 Cov.: 32 AF XY: 0.0621 AC XY: 4624 AN XY: 74484

Gnomad4 AFR AF: 0.0480

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.0881

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.0471

Gnomad4 OTH AF: 0.0595

Alfa AF: 0.0496 Hom.: 42

Bravo AF: 0.0706

Asia WGS AF: 0.137 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.60

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: rs11690232; hg19: chr2-227597841;