rs7543281

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BP2	NM_182972.3	c.1410C>T	p.Gly470Gly	synonymous_variant	Exon 2 of 2	ENST00000366609.4	NP_892017.2
IRF2BP2	NM_001077397.1	c.1362C>T	p.Gly454Gly	synonymous_variant	Exon 2 of 2		NP_001070865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BP2	ENST00000366609.4	c.1410C>T	p.Gly470Gly	synonymous_variant	Exon 2 of 2	1	NM_182972.3	ENSP00000355568.3
IRF2BP2	ENST00000366610.7	c.1362C>T	p.Gly454Gly	synonymous_variant	Exon 2 of 2	1		ENSP00000355569.3
IRF2BP2	ENST00000491430.1	n.423C>T		non_coding_transcript_exon_variant	Exon 2 of 2	1
ENSG00000228830	ENST00000436039.1	n.484G>A		non_coding_transcript_exon_variant	Exon 1 of 2	3

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

GnomAD3 exomes AF: 0.108 AC: 27150 AN: 251370 Hom.: 1659 AF XY: 0.110 AC XY: 14984 AN XY: 135860

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 SAS exome AF: 0.0802

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

Gnomad4 AFR exome AF: 0.0899

Gnomad4 AMR exome AF: 0.0615

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0198

Gnomad4 SAS exome AF: 0.0797

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.117

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

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.0821

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.117

Alfa AF: 0.134 Hom.: 1747

Bravo AF: 0.108

Asia WGS AF: 0.0530 AC: 184 AN: 3478

EpiCase AF: 0.137

EpiControl AF: 0.140

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.88
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7

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