NM_001570.4:c.94+249G>C

Variant names:

• chr3-10165297-G-C
• rs11465853
• NM_001570.4:c.94+249G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001570.4(IRAK2):​c.94+249G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,936 control chromosomes in the GnomAD database, including 7,914 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 0.32 (7914 hom., cov: 32)
• Consequence: IRAK2 NM_001570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• Publications: 6 publications found

Genes affected

IRAK2 (HGNC:6113): (interleukin 1 receptor associated kinase 2) IRAK2 encodes the interleukin-1 receptor-associated kinase 2, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. IRAK2 is reported to participate in the IL1-induced upregulation of NF-kappaB. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK2	NM_001570.4	c.94+249G>C		intron_variant	Intron 1 of 12	ENST00000256458.5	NP_001561.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK2	ENST00000256458.5	c.94+249G>C		intron_variant	Intron 1 of 12	1	NM_001570.4	ENSP00000256458.4

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48812 AN: 151818 Hom.: 7921 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.321 AC: 48824 AN: 151936 Hom.: 7914 Cov.: 32 AF XY: 0.321 AC XY: 23822 AN XY: 74258

African (AFR) AF: 0.310 AC: 12829 AN: 41432

American (AMR) AF: 0.312 AC: 4759 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 704 AN: 3472

East Asian (EAS) AF: 0.429 AC: 2207 AN: 5146

South Asian (SAS) AF: 0.418 AC: 2014 AN: 4814

European-Finnish (FIN) AF: 0.281 AC: 2969 AN: 10568

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22291 AN: 67936

Other (OTH) AF: 0.309 AC: 653 AN: 2112

Alfa AF: 0.331 Hom.: 1077

Bravo AF: 0.320

Asia WGS AF: 0.424 AC: 1476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.67
PhyloP100		0.40
PromoterAI		0.053	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.26		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11465853; hg19: chr3-10206981;