chr1-234609365-C-T

Variant names:

• chr1-234609365-C-T
• NM_182972.3:c.130G>A

Variant summary

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

The NM_182972.3(IRF2BP2):​c.130G>A​(p.Glu44Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRF2BP2 NM_182972.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.47
• Publications: 0 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]

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

ENSG00000228830 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182972.3. 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
	IRF2BP2	NM_182972.3	MANE Select	c.130G>A	p.Glu44Lys	missense	Exon 1 of 2	NP_892017.2	Q7Z5L9-1
	IRF2BP2	NM_001077397.1		c.130G>A	p.Glu44Lys	missense	Exon 1 of 2	NP_001070865.1	Q7Z5L9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2BP2	ENST00000366609.4	TSL:1 MANE Select	c.130G>A	p.Glu44Lys	missense	Exon 1 of 2	ENSP00000355568.3	Q7Z5L9-1
	IRF2BP2	ENST00000366610.8	TSL:1	c.130G>A	p.Glu44Lys	missense	Exon 1 of 2	ENSP00000355569.3	Q7Z5L9-2
	IRF2BP2	ENST00000947260.1		c.130G>A	p.Glu44Lys	missense	Exon 1 of 2	ENSP00000617319.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1400204 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 694872

African (AFR) AF: 0.00 AC: 0 AN: 28814

American (AMR) AF: 0.00 AC: 0 AN: 37982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24544

East Asian (EAS) AF: 0.00 AC: 0 AN: 32980

South Asian (SAS) AF: 0.00 AC: 0 AN: 79640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5138

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083898

Other (OTH) AF: 0.00 AC: 0 AN: 57658

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Pathogenic	0.61	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.5
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.59		Gain of ubiquitination at E44 (P = 0.0203)
MVP		0.63
MPC		2.4
ClinPred		0.99	D
GERP RS		1.8
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.69
gMVP		0.79
Mutation Taster		=32/68	disease causing

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

hg19: chr1-234745111;