NM_001569.4:c.1701A>G

Variant names:

• chrX-154013272-T-C
• rs3027905
• NM_001569.4:c.1701A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001569.4(IRAK1):​c.1701A>G​(p.Pro567Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,209,651 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., 4 hem., cov: 26)
  • Exomes 𝑓: 0.000023 (0 hom. 6 hem.)
• Consequence: IRAK1 NM_001569.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.714
• Publications: 1 publications found

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]

IRAK1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.02).
• BP6: Variant X-154013272-T-C is Benign according to our data. Variant chrX-154013272-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 753596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.714 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 4 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001569.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK1	NM_001569.4	MANE Select	c.1701A>G	p.Pro567Pro	synonymous	Exon 12 of 14	NP_001560.2	P51617-1
	IRAK1	NM_001410701.1		c.1689A>G	p.Pro563Pro	synonymous	Exon 11 of 13	NP_001397630.1	D3YTB5
	IRAK1	NM_001025242.2		c.1611A>G	p.Pro537Pro	synonymous	Exon 12 of 14	NP_001020413.1	P51617-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK1	ENST00000369980.8	TSL:1 MANE Select	c.1701A>G	p.Pro567Pro	synonymous	Exon 12 of 14	ENSP00000358997.3	P51617-1
	IRAK1	ENST00000393687.6	TSL:1	c.1611A>G	p.Pro537Pro	synonymous	Exon 12 of 14	ENSP00000377291.2	P51617-2
	IRAK1	ENST00000369974.6	TSL:1	c.1464A>G	p.Pro488Pro	synonymous	Exon 11 of 13	ENSP00000358991.2	P51617-4

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 18 AN: 113579 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000574

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000521 AC: 9 AN: 172631 AF XY: 0.0000157

Gnomad AFR exome AF: 0.000689

Gnomad AMR exome AF: 0.0000369

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000228 AC: 25 AN: 1096019 Hom.: 0 Cov.: 32 AF XY: 0.0000166 AC XY: 6 AN XY: 362317

African (AFR) AF: 0.000721 AC: 19 AN: 26367

American (AMR) AF: 0.0000569 AC: 2 AN: 35136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19349

East Asian (EAS) AF: 0.00 AC: 0 AN: 30194

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3862

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841708

Other (OTH) AF: 0.0000652 AC: 3 AN: 45979

GnomAD4 genome AF: 0.000158 AC: 18 AN: 113632 Hom.: 0 Cov.: 26 AF XY: 0.000112 AC XY: 4 AN XY: 35780

African (AFR) AF: 0.000573 AC: 18 AN: 31422

American (AMR) AF: 0.00 AC: 0 AN: 10902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3583

South Asian (SAS) AF: 0.00 AC: 0 AN: 2831

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6425

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53364

Other (OTH) AF: 0.00 AC: 0 AN: 1553

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000257

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.66
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism

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: rs3027905; hg19: chrX-153278723;