1-234609263-A-T

Variant names:

• chr1-234609263-A-T
• rs7545855
• NM_182972.3:c.232T>A

Variant summary

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

The ENST00000366609.4(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. 15/22 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 ENST00000366609.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495
• Publications: 20 publications found

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]

ENSG00000228830 (HGNC:):

LINC00184 (HGNC:37192): (long intergenic non-protein coding RNA 184)

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=0.07655713).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366609.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2BP2	NM_182972.3	MANE Select	c.232T>A	p.Ser78Thr	missense	Exon 1 of 2	NP_892017.2
	IRF2BP2	NM_001077397.1		c.232T>A	p.Ser78Thr	missense	Exon 1 of 2	NP_001070865.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2BP2	ENST00000366609.4	TSL:1 MANE Select	c.232T>A	p.Ser78Thr	missense	Exon 1 of 2	ENSP00000355568.3
	IRF2BP2	ENST00000366610.8	TSL:1	c.232T>A	p.Ser78Thr	missense	Exon 1 of 2	ENSP00000355569.3
	ENSG00000228830	ENST00000436039.1	TSL:3	n.631-158A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4724

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.49
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.020
Sift	Benign	0.20	T
Sift4G	Benign	0.45	T
Polyphen		0.0010	B
Vest4		0.057
MutPred		0.14		Gain of methylation at K82 (P = 0.0862)
MVP		0.44
MPC		1.1
ClinPred		0.087	T
GERP RS		0.22
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
Varity_R		0.075
gMVP		0.18
Mutation Taster		=98/2	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: rs7545855; hg19: chr1-234745009;