1-234609263-A-T

Position:

• chr1-234609263-A-T

Variant summary

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

The NM_182972.3(IRF2BP2):​c.232T>A​(p.Ser78Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S78P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IRF2BP2 NM_182972.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495

Genes affected

IRF2BP2 (HGNC:21729): (interferon regulatory factor 2 binding protein 2) This gene encodes an interferon regulatory factor-2 (IRF2) binding protein that interacts with the C-terminal transcriptional repression domain of IRF2. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

(HGNC:):

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=0.07655713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF2BP2	NM_182972.3	c.232T>A	p.Ser78Thr	missense_variant	1/2	ENST00000366609.4
IRF2BP2	NM_001077397.1	c.232T>A	p.Ser78Thr	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF2BP2	ENST00000366609.4	c.232T>A	p.Ser78Thr	missense_variant	1/2	1	NM_182972.3	P3
IRF2BP2	ENST00000366610.7	c.232T>A	p.Ser78Thr	missense_variant	1/2	1		A1
	ENST00000436039.1	n.631-158A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.77
DEOGEN2	Benign	0.0035	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.20	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.48	N;N
REVEL	Benign	0.020
Sift	Benign	0.20	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.0010	B;B
Vest4		0.057
MutPred		0.14		Gain of methylation at K82 (P = 0.0862);Gain of methylation at K82 (P = 0.0862);
MVP		0.44
MPC		1.1
ClinPred		0.087	T
GERP RS		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
Varity_R		0.075
gMVP		0.18

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: rs7545855; hg19: chr1-234745009;