3-10226333-C-T

Variant names:

• chr3-10226333-C-T
• rs779905
• NM_001570.4:c.1210-38C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001570.4(IRAK2):​c.1210-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,559,626 control chromosomes in the GnomAD database, including 36,996 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 0.23 (5020 hom., cov: 31)
  • Exomes 𝑓: 0.18 (31976 hom.)
• Consequence: IRAK2 NM_001570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK2	NM_001570.4	c.1210-38C>T		intron_variant	Intron 9 of 12	ENST00000256458.5	NP_001561.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK2	ENST00000256458.5	c.1210-38C>T		intron_variant	Intron 9 of 12	1	NM_001570.4	ENSP00000256458.4

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34488 AN: 151906 Hom.: 5013 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.226

GnomAD3 exomes AF: 0.249 AC: 61442 AN: 246826 Hom.: 10446 AF XY: 0.248 AC XY: 33178 AN XY: 133836

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.661

Gnomad SAS exome AF: 0.385

Gnomad FIN exome AF: 0.162

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.183 AC: 257278 AN: 1407600 Hom.: 31976 Cov.: 22 AF XY: 0.188 AC XY: 132154 AN XY: 702230

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.651

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.227 AC: 34516 AN: 152026 Hom.: 5020 Cov.: 31 AF XY: 0.235 AC XY: 17439 AN XY: 74304

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.226

Alfa AF: 0.160 Hom.: 1378

Bravo AF: 0.236

Asia WGS AF: 0.492 AC: 1706 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	0.24
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs779905; hg19: chr3-10268017; COSMIC: COSV56528820;