NM_001010844.4:c.62G>C

Variant names:

• chr6-78867638-G-C
• rs755760222
• NM_001010844.4:c.62G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010844.4(IRAK1BP1):​c.62G>C​(p.Arg21Pro) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IRAK1BP1 NM_001010844.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.759
• Publications: 2 publications found

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]

ENSG00000295662 (HGNC:):

ACMG classification

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=0.08632758).

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.62G>C	p.Arg21Pro	missense	Exon 1 of 4	NP_001010844.1	Q5VVH5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK1BP1	ENST00000369940.7	TSL:1 MANE Select	c.62G>C	p.Arg21Pro	missense	Exon 1 of 4	ENSP00000358956.1	Q5VVH5
	IRAK1BP1	ENST00000606868.5	TSL:1	n.32G>C		non_coding_transcript_exon	Exon 1 of 5	ENSP00000475570.1	U3KQ57
	ENSG00000295662	ENST00000731641.1		n.-148C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.4
DANN	Benign	0.84
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.76
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.13
Sift	Benign	0.12	T
Sift4G	Benign	0.33	T
Polyphen		0.0010	B
Vest4		0.41
MutPred		0.34		Loss of MoRF binding (P = 0.0399)
MVP		0.13
MPC		0.089
ClinPred		0.091	T
GERP RS		2.5
PromoterAI		-0.021	Neutral
Varity_R		0.15
gMVP		0.46
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs755760222; hg19: chr6-79577355;