dbSNP rs3027907: IRAK1:c.1539+48T>C (chrX-154013994-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001569.4(IRAK1):c.1539+48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,178,432 control chromosomes in the GnomAD database, including 835 homozygotes. There are 3,319 hemizygotes in GnomAD. 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 0.058 ( 443 hom., 1756 hem., cov: 23)

Exomes 𝑓: 0.0057 ( 392 hom. 1563 hem. )

Consequence

IRAK1
NM_001569.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK1	NM_001569.4 link	c.1539+48T>C		intron_variant	Intron 11 of 13	ENST00000369980.8	NP_001560.2	P51617-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK1	ENST00000369980.8 link	c.1539+48T>C		intron_variant	Intron 11 of 13	1	NM_001569.4	ENSP00000358997.3		P51617-1

Frequencies

GnomAD3 genomes

AF:

0.0574

AC:

6429

AN:

111943

Hom.:

442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0251

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000368

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.000509

Gnomad OTH

AF:

0.0502

GnomAD2 exomes

AF:

0.0156

AC:

1968

AN:

126066

AF XY:

0.0106

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.00869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000346

Gnomad OTH exome

AF:

0.00702

GnomAD4 exome

AF:

0.00573

AC:

6110

AN:

1066439

Hom.:

392

Cov.:

AF XY:

0.00453

AC XY:

1563

AN XY:

345289

show subpopulations

African (AFR)

AF:

0.201

AC:

5005

AN:

24935

American (AMR)

AF:

0.0108

AC:

310

AN:

28591

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18599

East Asian (EAS)

AF:

0.0000344

AC:

AN:

29109

South Asian (SAS)

AF:

0.000493

AC:

AN:

50694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38242

Middle Eastern (MID)

AF:

0.00801

AC:

AN:

2870

European-Non Finnish (NFE)

AF:

0.000216

AC:

179

AN:

828585

Other (OTH)

AF:

0.0127

AC:

567

AN:

44814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

190

379

569

758

948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<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:

0.0576

AC:

6456

AN:

111993

Hom.:

443

Cov.:

AF XY:

0.0513

AC XY:

1756

AN XY:

34245

show subpopulations

African (AFR)

AF:

0.198

AC:

6082

AN:

30758

American (AMR)

AF:

0.0250

AC:

268

AN:

10705

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3518

South Asian (SAS)

AF:

0.000369

AC:

AN:

2712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6205

Middle Eastern (MID)

AF:

0.00917

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000509

AC:

AN:

53012

Other (OTH)

AF:

0.0495

AC:

AN:

1534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

188

376

564

752

940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0464

Hom.:

217

Bravo

AF:

0.0676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.3

(source)

DANN

Benign

0.40

PhyloP100

0.0

PromoterAI

-0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over