NM_005544.3:c.*22-13591C>T

Variant names:

• chr2-226749841-G-A
• rs10205923
• NM_005544.3:c.*22-13591C>T

Variant summary

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

The NM_005544.3(IRS1):​c.*22-13591C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,068 control chromosomes in the GnomAD database, including 2,740 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 0.16 (2740 hom., cov: 32)
• Consequence: IRS1 NM_005544.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS1	NM_005544.3	c.*22-13591C>T		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.*22-13591C>T		intron_variant	Intron 1 of 1	1	NM_005544.3	ENSP00000304895.4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23978 AN: 151950 Hom.: 2729 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0554

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.158 AC: 24040 AN: 152068 Hom.: 2740 Cov.: 32 AF XY: 0.160 AC XY: 11876 AN XY: 74362

African (AFR) AF: 0.298 AC: 12348 AN: 41440

American (AMR) AF: 0.189 AC: 2890 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1574 AN: 5158

South Asian (SAS) AF: 0.216 AC: 1043 AN: 4824

European-Finnish (FIN) AF: 0.0554 AC: 586 AN: 10584

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4774 AN: 67990

Other (OTH) AF: 0.137 AC: 289 AN: 2108

Alfa AF: 0.105 Hom.: 1300

Bravo AF: 0.176

Asia WGS AF: 0.246 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		-0.27
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: rs10205923; hg19: chr2-227614557;