6-78898102-G-T

Variant names:

• chr6-78898102-G-T
• rs370888320
• NM_001010844.4:c.551G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010844.4(IRAK1BP1):​c.551G>T​(p.Arg184Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: IRAK1BP1 NM_001010844.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708

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]

ACMG classification

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=0.1912308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK1BP1	NM_001010844.4	c.551G>T	p.Arg184Leu	missense_variant	Exon 4 of 4	ENST00000369940.7	NP_001010844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK1BP1	ENST00000369940.7	c.551G>T	p.Arg184Leu	missense_variant	Exon 4 of 4	1	NM_001010844.4	ENSP00000358956.1
IRAK1BP1	ENST00000606868.5	n.482+143G>T		intron_variant	Intron 3 of 4	1		ENSP00000475570.1
IRAK1BP1	ENST00000607739.1	c.290G>T	p.Arg97Leu	missense_variant	Exon 4 of 5	2		ENSP00000475503.1
IRAK1BP1	ENST00000606929.1	c.-92G>T		upstream_gene_variant		5		ENSP00000475395.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250484 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460760 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726648

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000630

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000151

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	0.019
Eigen_PC	Benign	-0.041
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.80	N;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.6	N;.
REVEL	Benign	0.22
Sift	Benign	0.39	T;.
Sift4G	Uncertain	0.024	D;D
Polyphen		1.0	D;.
Vest4		0.22
MutPred		0.57		Loss of MoRF binding (P = 0.0106);.;
MVP		0.30
MPC		0.11
ClinPred		0.44	T
GERP RS		3.1
Varity_R		0.068
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs370888320; hg19: chr6-79607819; COSMIC: COSV64048291; COSMIC: COSV64048291;