chr1-234607141-G-C

Position:

• chr1-234607141-G-C

Variant summary

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

The NM_182972.3(IRF2BP2):​c.1760C>G​(p.Ser587Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S587S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IRF2BP2 NM_182972.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.94

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:):

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=0.4199093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF2BP2	NM_182972.3	c.1760C>G	p.Ser587Trp	missense_variant	2/2	ENST00000366609.4	NP_892017.2
IRF2BP2	NM_001077397.1	c.1712C>G	p.Ser571Trp	missense_variant	2/2		NP_001070865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF2BP2	ENST00000366609.4	c.1760C>G	p.Ser587Trp	missense_variant	2/2	1	NM_182972.3	ENSP00000355568.3
IRF2BP2	ENST00000366610.7	c.1712C>G	p.Ser571Trp	missense_variant	2/2	1		ENSP00000355569.3
ENSG00000228830	ENST00000436039.1	n.134G>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.0023	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	34
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.81	.;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.52
MutPred		0.20		.;Loss of phosphorylation at S587 (P = 0.0019);
MVP		0.67
MPC		0.59
ClinPred		1.0	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.66
gMVP		0.26

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: rs1571956509; hg19: chr1-234742887; COSMIC: COSV64015592; COSMIC: COSV64015592;