chr1-234607491-G-A

Variant names:

• chr1-234607491-G-A
• rs7543281
• NM_182972.3:c.1410C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182972.3(IRF2BP2):​c.1410C>T​(p.Gly470Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,614,126 control chromosomes in the GnomAD database, including 13,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1100 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12654 hom.)
• Consequence: IRF2BP2 NM_182972.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.499
• Publications: 10 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]

IRF2BP2 Gene-Disease associations (from GenCC):

• immunodeficiency, common variable, 14

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000228830 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 1-234607491-G-A is Benign according to our data. Variant chr1-234607491-G-A is described in ClinVar as Benign. ClinVar VariationId is 402981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.499 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2BP2	NM_182972.3	MANE Select	c.1410C>T	p.Gly470Gly	synonymous	Exon 2 of 2	NP_892017.2
	IRF2BP2	NM_001077397.1		c.1362C>T	p.Gly454Gly	synonymous	Exon 2 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.1410C>T	p.Gly470Gly	synonymous	Exon 2 of 2	ENSP00000355568.3
	IRF2BP2	ENST00000366610.8	TSL:1	c.1362C>T	p.Gly454Gly	synonymous	Exon 2 of 2	ENSP00000355569.3
	IRF2BP2	ENST00000491430.1	TSL:1	n.423C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17430 AN: 152146 Hom.: 1101 Cov.: 33

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0822

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.118

GnomAD2 exomes AF: 0.108 AC: 27150 AN: 251370 AF XY: 0.110

Gnomad AFR exome AF: 0.0908

Gnomad AMR exome AF: 0.0586

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.0262

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.128 AC: 186881 AN: 1461862 Hom.: 12654 Cov.: 33 AF XY: 0.127 AC XY: 92252 AN XY: 727232

African (AFR) AF: 0.0899 AC: 3010 AN: 33480

American (AMR) AF: 0.0615 AC: 2751 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3431 AN: 26136

East Asian (EAS) AF: 0.0198 AC: 787 AN: 39700

South Asian (SAS) AF: 0.0797 AC: 6873 AN: 86258

European-Finnish (FIN) AF: 0.133 AC: 7092 AN: 53406

Middle Eastern (MID) AF: 0.154 AC: 889 AN: 5768

European-Non Finnish (NFE) AF: 0.139 AC: 154989 AN: 1111996

Other (OTH) AF: 0.117 AC: 7059 AN: 60394

GnomAD4 genome AF: 0.114 AC: 17428 AN: 152264 Hom.: 1100 Cov.: 33 AF XY: 0.112 AC XY: 8364 AN XY: 74448

African (AFR) AF: 0.0917 AC: 3812 AN: 41554

American (AMR) AF: 0.0821 AC: 1256 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3472

East Asian (EAS) AF: 0.0258 AC: 134 AN: 5186

South Asian (SAS) AF: 0.0700 AC: 338 AN: 4830

European-Finnish (FIN) AF: 0.133 AC: 1415 AN: 10602

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9607 AN: 68000

Other (OTH) AF: 0.117 AC: 247 AN: 2112

Alfa AF: 0.130 Hom.: 2297

Bravo AF: 0.108

Asia WGS AF: 0.0530 AC: 184 AN: 3478

EpiCase AF: 0.137

EpiControl AF: 0.140

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		0.50
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs7543281; hg19: chr1-234743237; COSMIC: COSV64014934;