Variant rs4636 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182972.3(IRF2BP2):c.828G>T(p.Ala276=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,521,876 control chromosomes in the GnomAD database, including 94,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7665 hom., cov: 33)

Exomes 𝑓: 0.35 ( 86978 hom. )

Consequence

IRF2BP2
NM_182972.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.425

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 1-234608667-C-A is Benign according to our data. Variant chr1-234608667-C-A is described in ClinVar as [Benign]. Clinvar id is 402983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.425 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF2BP2	NM_182972.3 linkuse as main transcript	c.828G>T	p.Ala276=	synonymous_variant	1/2	ENST00000366609.4
IRF2BP2	NM_001077397.1 linkuse as main transcript	c.828G>T	p.Ala276=	synonymous_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF2BP2	ENST00000366609.4 linkuse as main transcript	c.828G>T	p.Ala276=	synonymous_variant	1/2	1	NM_182972.3	P3	Q7Z5L9-1
IRF2BP2	ENST00000366610.7 linkuse as main transcript	c.828G>T	p.Ala276=	synonymous_variant	1/2	1		A1	Q7Z5L9-2
	ENST00000436039.1 linkuse as main transcript	n.631-754C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46099

AN:

152042

Hom.:

7666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.332

GnomAD3 exomes

AF:

0.356

AC:

46831

AN:

131388

Hom.:

8469

AF XY:

0.358

AC XY:

26743

AN XY:

74636

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.304

Gnomad ASJ exome

AF:

0.436

Gnomad EAS exome

AF:

0.257

Gnomad SAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.393

Gnomad NFE exome

AF:

0.401

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.352

AC:

482618

AN:

1369716

Hom.:

86978

Cov.:

AF XY:

0.351

AC XY:

237540

AN XY:

677110

show subpopulations

Gnomad4 AFR exome

AF:

0.175

Gnomad4 AMR exome

AF:

0.299

Gnomad4 ASJ exome

AF:

0.419

Gnomad4 EAS exome

AF:

0.243

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.365

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.303

AC:

46106

AN:

152160

Hom.:

7665

Cov.:

AF XY:

0.305

AC XY:

22683

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.267

Gnomad4 FIN

AF:

0.373

Gnomad4 NFE

AF:

0.362

Gnomad4 OTH

AF:

0.332

Alfa

AF:

0.334

Hom.:

1574

Bravo

AF:

0.297

Asia WGS

AF:

0.247

AC:

860

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -

Immunodeficiency, common variable, 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.6

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over