rs1025333

Variant names:

• chr2-226780809-T-A
• rs1025333
• NM_005544.3:c.*21+14180A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-226780809-T-A
• chr2-226780809-T-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.*21+14180A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,222 control chromosomes in the GnomAD database, including 2,073 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 0.14 (2073 hom., cov: 32)
• Consequence: IRS1 NM_005544.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 6 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRS1	NM_005544.3	MANE Select	c.*21+14180A>T		intron	N/A	NP_005535.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRS1	ENST00000305123.6	TSL:1 MANE Select	c.*21+14180A>T		intron	N/A	ENSP00000304895.4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21748 AN: 152104 Hom.: 2067 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0744

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.143 AC: 21800 AN: 152222 Hom.: 2073 Cov.: 32 AF XY: 0.144 AC XY: 10721 AN XY: 74426

African (AFR) AF: 0.239 AC: 9905 AN: 41502

American (AMR) AF: 0.189 AC: 2886 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1310 AN: 5180

South Asian (SAS) AF: 0.232 AC: 1115 AN: 4816

European-Finnish (FIN) AF: 0.0538 AC: 571 AN: 10610

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0744 AC: 5063 AN: 68032

Other (OTH) AF: 0.136 AC: 286 AN: 2110

Alfa AF: 0.111 Hom.: 177

Bravo AF: 0.159

Asia WGS AF: 0.231 AC: 800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.24
DANN	Benign	0.83
PhyloP100		-0.40
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: rs1025333; hg19: chr2-227645525;