Variant 6-78885405-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010844.4(IRAK1BP1):c.343T>C(p.Phe115Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 1,584,212 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 1 hom. )

Consequence

IRAK1BP1
NM_001010844.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

IRAK1BP1 (HGNC:17368): (interleukin 1 receptor associated kinase 1 binding protein 1) Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

IRAK1BP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14615619).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK1BP1	NM_001010844.4 linkuse as main transcript	c.343T>C	p.Phe115Leu	missense_variant	2/4	ENST00000369940.7	NP_001010844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
IRAK1BP1	ENST00000369940.7 linkuse as main transcript	c.343T>C	p.Phe115Leu	missense_variant	2/4	1	NM_001010844.4	ENSP00000358956	P1
IRAK1BP1	ENST00000606868.5 linkuse as main transcript	c.313T>C	p.Phe105Leu	missense_variant, NMD_transcript_variant	2/5	1		ENSP00000475570
IRAK1BP1	ENST00000607739.1 linkuse as main transcript	c.82T>C	p.Phe28Leu	missense_variant	2/5	2		ENSP00000475503

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151278

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000389

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

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

GnomAD3 exomes

AF:

0.0000416

AC:

AN:

240462

Hom.:

AF XY:

0.0000306

AC XY:

AN XY:

130528

show subpopulations

Gnomad AFR exome

AF:

0.000507

Gnomad AMR exome

AF:

0.0000652

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:

0.0000161

AC:

AN:

1432816

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

714472

show subpopulations

Gnomad4 AFR exome

AF:

0.000336

Gnomad4 AMR exome

AF:

0.0000477

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:

0.00000917

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000112

AC:

AN:

151396

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

73928

show subpopulations

Gnomad4 AFR

AF:

0.000387

Gnomad4 AMR

AF:

0.0000661

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000178

Hom.:

Bravo

AF:

0.000147

ExAC

AF:

0.0000330

AC:

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

Jan 10, 2022

The c.343T>C (p.F115L) alteration is located in exon 2 (coding exon 2) of the IRAK1BP1 gene. This alteration results from a T to C substitution at nucleotide position 343, causing the phenylalanine (F) at amino acid position 115 to be replaced by a leucine (L). 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

Pathogenic

0.70

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.80

N;.

MutationTaster

Benign

0.90

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.70

N;.

REVEL

Benign

0.14

Sift

Benign

0.89

T;.

Sift4G

Benign

0.33

T;T

Polyphen

0.027

B;.

Vest4

0.57

MutPred

0.42

Loss of methylation at K113 (P = 0.1084);.;

MVP

0.29

MPC

0.091

ClinPred

0.0059

GERP RS

2.7

Varity_R

0.057

gMVP

0.31

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