rs11690232

Variant names:

• chr2-226733125-T-C
• rs11690232
• NM_005544.3:c.*3147A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005544.3. 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
	IRS1	NM_005544.3	MANE Select	c.*3147A>G		3_prime_UTR	Exon 2 of 2	NP_005535.1	P35568

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRS1	ENST00000305123.6	TSL:1 MANE Select	c.*3147A>G		3_prime_UTR	Exon 2 of 2	ENSP00000304895.4	P35568

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0480 AC: 1996 AN: 41558

American (AMR) AF: 0.115 AC: 1765 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0881 AC: 306 AN: 3472

East Asian (EAS) AF: 0.188 AC: 972 AN: 5172

South Asian (SAS) AF: 0.140 AC: 674 AN: 4830

European-Finnish (FIN) AF: 0.0173 AC: 184 AN: 10626

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0471 AC: 3207 AN: 68030

Other (OTH) AF: 0.0595 AC: 126 AN: 2116

Alfa AF: 0.0606 Hom.: 130

Bravo AF: 0.0706

Asia WGS AF: 0.137 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.60
PhyloP100		-0.32
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: rs11690232; hg19: chr2-227597841;