Genetic Variant NM_001569.4:c.1854C>T (chrX-154013119-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001569.4(IRAK1):c.1854C>T(p.Ala618Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,208,653 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 0.000053 ( 0 hom., 1 hem., cov: 27)

Exomes 𝑓: 0.000028 ( 0 hom. 9 hem. )

Consequence

IRAK1
NM_001569.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.43

Publications

0 publications found

Variant links:

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

IRAK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (REVEL=0.051).

BP6

Variant X-154013119-G-A is Benign according to our data. Variant chrX-154013119-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3771450.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.42 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 9 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IRAK1	NM_001569.4	MANE Select	c.1854C>T	p.Ala618Ala	synonymous	Exon 12 of 14	NP_001560.2	P51617-1
IRAK1	NM_001410701.1		c.1842C>T	p.Ala614Ala	synonymous	Exon 11 of 13	NP_001397630.1	D3YTB5
IRAK1	NM_001025242.2		c.1764C>T	p.Ala588Ala	synonymous	Exon 12 of 14	NP_001020413.1	P51617-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IRAK1	ENST00000369980.8	TSL:1 MANE Select	c.1854C>T	p.Ala618Ala	synonymous	Exon 12 of 14	ENSP00000358997.3	P51617-1
IRAK1	ENST00000393687.6	TSL:1	c.1764C>T	p.Ala588Ala	synonymous	Exon 12 of 14	ENSP00000377291.2	P51617-2
IRAK1	ENST00000369974.6	TSL:1	c.1617C>T	p.Ala539Ala	synonymous	Exon 11 of 13	ENSP00000358991.2	P51617-4

Frequencies

GnomAD3 genomes

AF:

0.0000529

AC:

AN:

113429

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000320

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000184

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:

0.0000563

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000514

AC:

AN:

175128

AF XY:

0.0000156

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000259

Gnomad OTH exome

AF:

0.000459

GnomAD4 exome

AF:

0.0000283

AC:

AN:

1095224

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

361806

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26332

American (AMR)

AF:

0.000114

AC:

AN:

35108

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19350

East Asian (EAS)

AF:

0.00

AC:

AN:

30139

South Asian (SAS)

AF:

0.000111

AC:

AN:

53889

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3316

European-Non Finnish (NFE)

AF:

0.0000202

AC:

AN:

841583

Other (OTH)

AF:

0.0000871

AC:

AN:

45937

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000529

AC:

AN:

113429

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

35567

show subpopulations

African (AFR)

AF:

0.0000320

AC:

AN:

31291

American (AMR)

AF:

0.000184

AC:

AN:

10856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2662

East Asian (EAS)

AF:

0.00

AC:

AN:

3614

South Asian (SAS)

AF:

0.00

AC:

AN:

2850

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6371

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000563

AC:

AN:

53328

Other (OTH)

AF:

0.00

AC:

AN:

1536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.3

(source)

DANN

Benign

0.71

PhyloP100

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over