rs8722

Variant names:

• chr1-234608504-G-A
• rs8722
• NM_182972.3:c.991C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-234608504-G-A
• chr1-234608504-G-C

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.991C>T​(p.Leu331Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,608,560 control chromosomes in the GnomAD database, including 38,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2668 hom., cov: 33)
  • Exomes 𝑓: 0.22 (36171 hom.)
• Consequence: IRF2BP2 NM_182972.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.511

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=-0.57).
• BP6: Variant 1-234608504-G-A is Benign according to our data. Variant chr1-234608504-G-A is described in ClinVar as [Benign]. Clinvar id is 402982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.511 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BP2	NM_182972.3	c.991C>T	p.Leu331Leu	synonymous_variant	Exon 1 of 2	ENST00000366609.4	NP_892017.2
IRF2BP2	NM_001077397.1	c.991C>T	p.Leu331Leu	synonymous_variant	Exon 1 of 2		NP_001070865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BP2	ENST00000366609.4	c.991C>T	p.Leu331Leu	synonymous_variant	Exon 1 of 2	1	NM_182972.3	ENSP00000355568.3
IRF2BP2	ENST00000366610.7	c.991C>T	p.Leu331Leu	synonymous_variant	Exon 1 of 2	1		ENSP00000355569.3
ENSG00000228830	ENST00000436039.1	n.630+867G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25369 AN: 152106 Hom.: 2671 Cov.: 33

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.189

GnomAD3 exomes AF: 0.189 AC: 45928 AN: 242520 Hom.: 4970 AF XY: 0.192 AC XY: 25291 AN XY: 131958

Gnomad AFR exome AF: 0.0345

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.231

Gnomad EAS exome AF: 0.204

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.216 AC: 315187 AN: 1456336 Hom.: 36171 Cov.: 32 AF XY: 0.213 AC XY: 154599 AN XY: 724136

Gnomad4 AFR exome AF: 0.0353

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.167 AC: 25361 AN: 152224 Hom.: 2668 Cov.: 33 AF XY: 0.167 AC XY: 12408 AN XY: 74406

Gnomad4 AFR AF: 0.0423

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.189

Alfa AF: 0.210 Hom.: 5404

Bravo AF: 0.158

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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: Frequency -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 31. Only high quality variants are reported. -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs8722; hg19: chr1-234744250; COSMIC: COSV64014695; COSMIC: COSV64014695;