rs7545855

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182972.3(IRF2BP2):c.232T>C(p.Ser78Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,377,458 control chromosomes in the GnomAD database, including 352,861 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 41039 hom., cov: 32)

Exomes 𝑓: 0.71 ( 311822 hom. )

Consequence

IRF2BP2
NM_182972.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.495

Publications

20 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 links:

ENSG00000228830 (HGNC:):

ENSG00000228830 links:

LINC00184 (HGNC:37192): (long intergenic non-protein coding RNA 184)

LINC00184 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3392341E-6).

BP6

Variant 1-234609263-A-G is Benign according to our data. Variant chr1-234609263-A-G is described in ClinVar as [Benign]. Clinvar id is 402984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BP2	NM_182972.3 link	c.232T>C	p.Ser78Pro	missense_variant	Exon 1 of 2	ENST00000366609.4	NP_892017.2	Q7Z5L9-1
IRF2BP2	NM_001077397.1 link	c.232T>C	p.Ser78Pro	missense_variant	Exon 1 of 2		NP_001070865.1	Q7Z5L9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IRF2BP2	ENST00000366609.4 link	c.232T>C	p.Ser78Pro	missense_variant	Exon 1 of 2	1	NM_182972.3	ENSP00000355568.3	Q7Z5L9-1
IRF2BP2	ENST00000366610.8 link	c.232T>C	p.Ser78Pro	missense_variant	Exon 1 of 2	1		ENSP00000355569.3	Q7Z5L9-2
ENSG00000228830	ENST00000436039.1 link	n.631-158A>G		intron_variant	Intron 1 of 1	3
LINC00184	ENST00000796406.1 link	n.-32A>G		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.728

AC:

109668

AN:

150662

Hom.:

41000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.842

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.622

Gnomad ASJ

AF:

0.749

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.487

Gnomad FIN

AF:

0.715

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.735

Gnomad OTH

AF:

0.734

GnomAD2 exomes

AF:

0.610

AC:

11605

AN:

19032

AF XY:

0.611

show subpopulations

Gnomad AFR exome

AF:

0.760

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.701

Gnomad EAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.725

Gnomad NFE exome

AF:

0.696

Gnomad OTH exome

AF:

0.666

GnomAD4 exome

AF:

0.707

AC:

867342

AN:

1226686

Hom.:

311822

Cov.:

AF XY:

0.702

AC XY:

420732

AN XY:

599294

show subpopulations

African (AFR)

AF:

0.840

AC:

20255

AN:

24126

American (AMR)

AF:

0.517

AC:

6135

AN:

11870

Ashkenazi Jewish (ASJ)

AF:

0.746

AC:

12756

AN:

17100

East Asian (EAS)

AF:

0.278

AC:

7607

AN:

27382

South Asian (SAS)

AF:

0.499

AC:

27234

AN:

54596

European-Finnish (FIN)

AF:

0.718

AC:

27126

AN:

37798

Middle Eastern (MID)

AF:

0.731

AC:

2533

AN:

3466

European-Non Finnish (NFE)

AF:

0.729

AC:

729211

AN:

1000446

Other (OTH)

AF:

0.691

AC:

34485

AN:

49902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

14644

29288

43933

58577

73221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.728

AC:

109756

AN:

150772

Hom.:

41039

Cov.:

AF XY:

0.718

AC XY:

52866

AN XY:

73584

show subpopulations

African (AFR)

AF:

0.842

AC:

34825

AN:

41372

American (AMR)

AF:

0.621

AC:

9443

AN:

15194

Ashkenazi Jewish (ASJ)

AF:

0.749

AC:

2580

AN:

3446

East Asian (EAS)

AF:

0.272

AC:

1357

AN:

4992

South Asian (SAS)

AF:

0.488

AC:

2339

AN:

4794

European-Finnish (FIN)

AF:

0.715

AC:

7402

AN:

10356

Middle Eastern (MID)

AF:

0.736

AC:

212

AN:

288

European-Non Finnish (NFE)

AF:

0.735

AC:

49477

AN:

67338

Other (OTH)

AF:

0.730

AC:

1525

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1422

2844

4265

5687

7109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.732

Hom.:

4724

Bravo

AF:

0.723

ExAC

AF:

0.361

AC:

11334

Asia WGS

AF:

0.416

AC:

1389

AN:

3326

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 72% of patients studied by a panel of primary immunodeficiencies. Number of patients: 68. 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

- -

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

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.2

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.0037

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.17

T;T

MetaRNN

Benign

0.0000013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

PhyloP100

0.49

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

1.8

N;N

REVEL

Benign

0.028

Sift

Benign

1.0

T;T

Sift4G

Benign

0.95

T;T

Polyphen

0.0

B;B

Vest4

0.048

MPC

1.5

ClinPred

0.0033

GERP RS

0.22

PromoterAI

-0.11

Neutral

(source)

Varity_R

0.099

gMVP

0.15

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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rs7545855

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