rs12052364

Variant names:

• chr2-226770492-A-G
• rs12052364
• NM_005544.3:c.*21+24497T>C

Variant summary

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

The NM_005544.3(IRS1):​c.*21+24497T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0493 in 152,302 control chromosomes in the GnomAD database, including 342 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 0.049 (342 hom., cov: 32)
• Consequence: IRS1 NM_005544.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS1	NM_005544.3	c.*21+24497T>C		intron_variant	Intron 1 of 1	ENST00000305123.6	NP_005535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRS1	ENST00000305123.6	c.*21+24497T>C		intron_variant	Intron 1 of 1	1	NM_005544.3	ENSP00000304895.4

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7507 AN: 152184 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0568

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

GnomAD4 genome AF: 0.0493 AC: 7508 AN: 152302 Hom.: 342 Cov.: 32 AF XY: 0.0503 AC XY: 3750 AN XY: 74484

African (AFR) AF: 0.0111 AC: 460 AN: 41572

American (AMR) AF: 0.113 AC: 1726 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3472

East Asian (EAS) AF: 0.174 AC: 899 AN: 5180

South Asian (SAS) AF: 0.127 AC: 613 AN: 4826

European-Finnish (FIN) AF: 0.0174 AC: 185 AN: 10618

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0457 AC: 3106 AN: 68016

Other (OTH) AF: 0.0562 AC: 119 AN: 2116

Alfa AF: 0.0565 Hom.: 81

Bravo AF: 0.0573

Asia WGS AF: 0.126 AC: 435 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.4
DANN	Benign	0.61
PhyloP100		0.41
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: rs12052364; hg19: chr2-227635208;