rs4636

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182972.3(IRF2BP2):c.828G>T(p.Ala276Ala) 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:5

Conservation

PhyloP100: -0.425

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency, common variable, 14
Inheritance: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

IRF2BP2 links:

ENSG00000228830 (HGNC:):

ENSG00000228830 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
IRF2BP2	NM_182972.3 link	c.828G>T	p.Ala276Ala	synonymous_variant	Exon 1 of 2	ENST00000366609.4	NP_892017.2
IRF2BP2	NM_001077397.1 link	c.828G>T	p.Ala276Ala	synonymous_variant	Exon 1 of 2		NP_001070865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
IRF2BP2	ENST00000366609.4 link	c.828G>T	p.Ala276Ala	synonymous_variant	Exon 1 of 2	1	NM_182972.3	ENSP00000355568.3
IRF2BP2	ENST00000366610.8 link	c.828G>T	p.Ala276Ala	synonymous_variant	Exon 1 of 2	1		ENSP00000355569.3
ENSG00000228830	ENST00000436039.1 link	n.631-754C>A		intron_variant	Intron 1 of 1	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

GnomAD2 exomes

AF:

0.356

AC:

46831

AN:

131388

AF XY:

0.358

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 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

African (AFR)

AF:

0.175

AC:

4886

AN:

27930

American (AMR)

AF:

0.299

AC:

9793

AN:

32804

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

9860

AN:

23514

East Asian (EAS)

AF:

0.243

AC:

8017

AN:

32968

South Asian (SAS)

AF:

0.282

AC:

21506

AN:

76374

European-Finnish (FIN)

AF:

0.365

AC:

13963

AN:

38230

Middle Eastern (MID)

AF:

0.386

AC:

1755

AN:

4546

European-Non Finnish (NFE)

AF:

0.365

AC:

393001

AN:

1076562

Other (OTH)

AF:

0.349

AC:

19837

AN:

56788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

18584

37169

55753

74338

92922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12432

24864

37296

49728

62160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.303

AC:

46106

AN:

152160

Hom.:

7665

Cov.:

AF XY:

0.305

AC XY:

22683

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.180

AC:

7470

AN:

41538

American (AMR)

AF:

0.334

AC:

5103

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

1471

AN:

3468

East Asian (EAS)

AF:

0.220

AC:

1139

AN:

5176

South Asian (SAS)

AF:

0.267

AC:

1292

AN:

4832

European-Finnish (FIN)

AF:

0.373

AC:

3949

AN:

10586

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.362

AC:

24588

AN:

67954

Other (OTH)

AF:

0.332

AC:

702

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1618

3235

4853

6470

8088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

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 -

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

- -

Immunodeficiency, common variable, 14

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.6

(source)

DANN

Benign

0.91

PhyloP100

-0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over