rs140583367

Variant names:

• chrX-154013331-C-A
• rs140583367
• NM_001569.4:c.1642G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-154013331-C-A
• chrX-154013331-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001569.4(IRAK1):​c.1642G>T​(p.Val548Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000916 in 1,092,164 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: IRAK1 NM_001569.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

Genes affected

IRAK1 (HGNC:6112): (interleukin 1 receptor associated kinase 1) This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057964742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK1	NM_001569.4	c.1642G>T	p.Val548Leu	missense_variant	Exon 12 of 14	ENST00000369980.8	NP_001560.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK1	ENST00000369980.8	c.1642G>T	p.Val548Leu	missense_variant	Exon 12 of 14	1	NM_001569.4	ENSP00000358997.3

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD3 exomes AF: 0.0000118 AC: 2 AN: 169029 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 59311

Gnomad AFR exome AF: 0.000168

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.16e-7 AC: 1 AN: 1092164 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 359036

Gnomad4 AFR exome AF: 0.0000383

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

Bravo AF: 0.00000756

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.010
DANN	Benign	0.89
DEOGEN2	Benign	0.077	T;.;.;T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.058	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	L;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.61	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.098	T;T;T;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.18	B;B;B;.
Vest4		0.064
MutPred		0.12		Loss of glycosylation at S549 (P = 0.1204);.;.;.;
MVP		0.60
MPC		0.53
ClinPred		0.026	T
GERP RS		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.083
gMVP		0.16

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: rs140583367; hg19: chrX-153278782;