6-78885405-T-G

Variant names:

• chr6-78885405-T-G
• rs536432481
• NM_001010844.4:c.343T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001010844.4(IRAK1BP1):​c.343T>G​(p.Phe115Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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: 33)
• Consequence: IRAK1BP1 NM_001010844.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3824272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK1BP1	NM_001010844.4	c.343T>G	p.Phe115Val	missense_variant	Exon 2 of 4	ENST00000369940.7	NP_001010844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK1BP1	ENST00000369940.7	c.343T>G	p.Phe115Val	missense_variant	Exon 2 of 4	1	NM_001010844.4	ENSP00000358956.1
IRAK1BP1	ENST00000606868.5	n.313T>G		non_coding_transcript_exon_variant	Exon 2 of 5	1		ENSP00000475570.1
IRAK1BP1	ENST00000607739.1	c.82T>G	p.Phe28Val	missense_variant	Exon 2 of 5	2		ENSP00000475503.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.097
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.12
Sift	Benign	0.31	T;.
Sift4G	Benign	0.28	T;T
Polyphen		0.064	B;.
Vest4		0.62
MutPred		0.48		Loss of ubiquitination at K113 (P = 0.0613);.;
MVP		0.25
MPC		0.10
ClinPred		0.16	T
GERP RS		2.7
Varity_R		0.079
gMVP		0.44

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

Other links and lift over

dbSNP: rs536432481; hg19: chr6-79595122;