rs10181778

Variant names:

• chr2-226749521-A-T
• rs10181778
• NM_005544.3:c.*22-13271T>A

Variant summary

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

The NM_005544.3(IRS1):​c.*22-13271T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,218 control chromosomes in the GnomAD database, including 679 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 0.083 (679 hom., cov: 32)
• Consequence: IRS1 NM_005544.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 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.*22-13271T>A		intron	N/A	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.*22-13271T>A		intron	N/A	ENSP00000304895.4	P35568

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12551 AN: 152100 Hom.: 676 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0779

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

GnomAD4 genome AF: 0.0826 AC: 12575 AN: 152218 Hom.: 679 Cov.: 32 AF XY: 0.0828 AC XY: 6161 AN XY: 74430

African (AFR) AF: 0.124 AC: 5156 AN: 41522

American (AMR) AF: 0.126 AC: 1929 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3470

East Asian (EAS) AF: 0.180 AC: 931 AN: 5166

South Asian (SAS) AF: 0.130 AC: 627 AN: 4820

European-Finnish (FIN) AF: 0.0173 AC: 184 AN: 10624

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0467 AC: 3178 AN: 68006

Other (OTH) AF: 0.0771 AC: 163 AN: 2114

Alfa AF: 0.0641 Hom.: 55

Bravo AF: 0.0952

Asia WGS AF: 0.135 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.036
DANN	Benign	0.26
PhyloP100		-1.7
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10181778;

hg19: chr2-227614237;