Genetic Variant IRAK1BP1:p.Val193Leu (chr6-78898128-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010844.4(IRAK1BP1):c.577G>C(p.Val193Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V193F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IRAK1BP1
NM_001010844.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.211649).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010844.4. 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
	IRAK1BP1	NM_001010844.4	MANE Select	c.577G>C	p.Val193Leu	missense	Exon 4 of 4	NP_001010844.1	Q5VVH5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IRAK1BP1	ENST00000369940.7	TSL:1 MANE Select	c.577G>C	p.Val193Leu	missense	Exon 4 of 4	ENSP00000358956.1	Q5VVH5
IRAK1BP1	ENST00000606868.5	TSL:1	n.482+169G>C		intron	N/A	ENSP00000475570.1	U3KQ57
IRAK1BP1	ENST00000607739.1	TSL:2	c.316G>C	p.Val106Leu	missense	Exon 4 of 5	ENSP00000475503.1	U3KQ34

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461722

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111956

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

0.00031

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0063

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.011

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.76

M_CAP

Benign

0.0026

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

2.3

PrimateAI

Benign

0.48

PROVEAN

Benign

0.45

REVEL

Benign

0.16

Sift

Benign

0.64

Sift4G

Benign

0.85

Polyphen

0.11

Vest4

0.055

MutPred

0.61

Loss of catalytic residue at Q195 (P = 0.0296)

MVP

0.45

MPC

0.15

ClinPred

0.67

GERP RS

4.0

PromoterAI

-0.0020

Neutral

(source)

Varity_R

0.054

gMVP

0.24

Mutation Taster

=94/6

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over