chr3-10195613-G-A

Variant names:

• chr3-10195613-G-A
• rs263408
• NM_001570.4:c.278-4756G>A

Variant summary

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

The NM_001570.4(IRAK2):​c.278-4756G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 152,184 control chromosomes in the GnomAD database, including 66,936 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 0.94 (66936 hom., cov: 29)
• Consequence: IRAK2 NM_001570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001570.4. 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
	IRAK2	NM_001570.4	MANE Select	c.278-4756G>A		intron	N/A	NP_001561.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK2	ENST00000256458.5	TSL:1 MANE Select	c.278-4756G>A		intron	N/A	ENSP00000256458.4

Frequencies

GnomAD3 genomes AF: 0.937 AC: 142512 AN: 152066 Hom.: 66872 Cov.: 29

Gnomad AFR AF: 0.980

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.928

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

GnomAD4 genome AF: 0.937 AC: 142634 AN: 152184 Hom.: 66936 Cov.: 29 AF XY: 0.938 AC XY: 69759 AN XY: 74406

African (AFR) AF: 0.980 AC: 40669 AN: 41516

American (AMR) AF: 0.914 AC: 13955 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 3285 AN: 3472

East Asian (EAS) AF: 0.929 AC: 4818 AN: 5184

South Asian (SAS) AF: 0.899 AC: 4331 AN: 4820

European-Finnish (FIN) AF: 0.965 AC: 10223 AN: 10598

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62247 AN: 68002

Other (OTH) AF: 0.928 AC: 1960 AN: 2112

Alfa AF: 0.921 Hom.: 123062

Bravo AF: 0.938

Asia WGS AF: 0.893 AC: 3106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.039
DANN	Benign	0.77
PhyloP100		-1.7
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: rs263408; hg19: chr3-10237297;