Variant X-154011911-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000369980.8(IRAK1):c.2087G>A(p.Gly696Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,208,157 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. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000026 ( 0 hom. 10 hem. )

Consequence

IRAK1
ENST00000369980.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.443

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019164711).

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK1	NM_001569.4 linkuse as main transcript	c.2087G>A	p.Gly696Asp	missense_variant	14/14	ENST00000369980.8	NP_001560.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAK1	ENST00000369980.8 linkuse as main transcript	c.2087G>A	p.Gly696Asp	missense_variant	14/14	1	NM_001569.4	ENSP00000358997	P1	P51617-1

Frequencies

GnomAD3 genomes

AF:

0.0000529

AC:

AN:

113362

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35488

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00187

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

181502

Hom.:

AF XY:

0.0000753

AC XY:

AN XY:

66360

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000489

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000256

AC:

AN:

1094795

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

360547

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000878

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000256

Gnomad4 NFE exome

AF:

0.00000952

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.0000529

AC:

AN:

113362

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00187

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000187

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2023

The c.2087G>A (p.G696D) alteration is located in exon 14 (coding exon 14) of the IRAK1 gene. This alteration results from a G to A substitution at nucleotide position 2087, causing the glycine (G) at amino acid position 696 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.026

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.30

M_CAP

Benign

0.0087

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N;N

PROVEAN

Benign

-0.49

REVEL

Benign

0.013

Sift

Benign

0.15

Sift4G

Benign

0.087

MVP

0.64

ClinPred

0.037

GERP RS

0.042

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over