rs10498210

Variant names:

• chr2-226755230-G-A
• rs10498210
• NM_005544.3:c.*22-18980C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-226755230-G-A
• chr2-226755230-G-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.*22-18980C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 152,182 control chromosomes in the GnomAD database, including 1,125 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 0.088 (1125 hom., cov: 33)
• Consequence: IRS1 NM_005544.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 9 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 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.*22-18980C>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.*22-18980C>T		intron	N/A	ENSP00000304895.4

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13397 AN: 152064 Hom.: 1119 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.0787

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0681

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

GnomAD4 genome AF: 0.0883 AC: 13444 AN: 152182 Hom.: 1125 Cov.: 33 AF XY: 0.0881 AC XY: 6553 AN XY: 74414

African (AFR) AF: 0.220 AC: 9114 AN: 41496

American (AMR) AF: 0.0693 AC: 1060 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3470

East Asian (EAS) AF: 0.0789 AC: 409 AN: 5182

South Asian (SAS) AF: 0.0871 AC: 420 AN: 4820

European-Finnish (FIN) AF: 0.0381 AC: 404 AN: 10602

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0258 AC: 1757 AN: 68008

Other (OTH) AF: 0.0697 AC: 147 AN: 2108

Alfa AF: 0.0354 Hom.: 52

Bravo AF: 0.0955

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.7
DANN	Benign	0.88
PhyloP100		0.11
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: rs10498210; hg19: chr2-227619946;