Variant 6-78885379-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 NM_001010844.4(IRAK1BP1):c.317C>T(p.Ala106Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000734 in 1,565,478 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 4 hom. )

Consequence

IRAK1BP1
NM_001010844.4 missense, splice_region

Scores

Splicing: ADA: 0.007742

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009795666).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK1BP1	NM_001010844.4 linkuse as main transcript	c.317C>T	p.Ala106Val	missense_variant, splice_region_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.317C>T	p.Ala106Val	missense_variant, splice_region_variant	2/4	1	NM_001010844.4	ENSP00000358956	P1
IRAK1BP1	ENST00000606868.5 linkuse as main transcript	c.287C>T	p.Ala96Val	missense_variant, splice_region_variant, NMD_transcript_variant	2/5	1		ENSP00000475570
IRAK1BP1	ENST00000607739.1 linkuse as main transcript	c.56C>T	p.Ala19Val	missense_variant, splice_region_variant	2/5	2		ENSP00000475503

Frequencies

GnomAD3 genomes

AF:

0.000751

AC:

114

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000884

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00105

AC:

252

AN:

239122

Hom.:

AF XY:

0.00109

AC XY:

141

AN XY:

129656

show subpopulations

Gnomad AFR exome

AF:

0.0000633

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.00823

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000651

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000958

Gnomad OTH exome

AF:

0.00138

GnomAD4 exome

AF:

0.000732

AC:

1035

AN:

1413480

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

550

AN XY:

705752

show subpopulations

Gnomad4 AFR exome

AF:

0.0000932

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00688

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000749

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000621

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000750

AC:

114

AN:

151998

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000884

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00123

Hom.:

Bravo

AF:

0.000733

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00108

AC:

131

EpiCase

AF:

0.00154

EpiControl

AF:

0.00180

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

Jul 29, 2023

The c.317C>T (p.A106V) alteration is located in exon 2 (coding exon 2) of the IRAK1BP1 gene. This alteration results from a C to T substitution at nucleotide position 317, causing the alanine (A) at amino acid position 106 to be replaced by a valine (V). 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

0.093

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.053

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.0057

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.62

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.025

Sift

Benign

0.18

T;.

Sift4G

Benign

0.19

T;T

Polyphen

0.085

B;.

Vest4

0.25

MVP

0.31

MPC

0.063

ClinPred

0.0094

GERP RS

4.3

Varity_R

0.041

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0077

dbscSNV1_RF

Benign

0.040

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