rs13431554

Variant names:

• chr2-226732872-A-G
• rs13431554
• NM_005544.3:c.*3400T>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.*3400T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,112 control chromosomes in the GnomAD database, including 1,204 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 0.10 (1204 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: IRS1 NM_005544.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS1	NM_005544.3	c.*3400T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000305123.6	NP_005535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRS1	ENST00000305123.6	c.*3400T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_005544.3	ENSP00000304895.4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15773 AN: 151982 Hom.: 1199 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0848

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0895

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.125 AC: 1 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.104 AC: 15814 AN: 152100 Hom.: 1204 Cov.: 32 AF XY: 0.104 AC XY: 7720 AN XY: 74370

African (AFR) AF: 0.193 AC: 8018 AN: 41476

American (AMR) AF: 0.135 AC: 2056 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 325 AN: 3470

East Asian (EAS) AF: 0.188 AC: 973 AN: 5162

South Asian (SAS) AF: 0.140 AC: 674 AN: 4826

European-Finnish (FIN) AF: 0.0175 AC: 185 AN: 10592

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0485 AC: 3296 AN: 67992

Other (OTH) AF: 0.0885 AC: 187 AN: 2112

Alfa AF: 0.0724 Hom.: 898

Bravo AF: 0.120

Asia WGS AF: 0.150 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.29
PhyloP100		-1.9
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: rs13431554; hg19: chr2-227597588;