Genetic Variant IRF2:c.-7+521G>A (chr4-184473858-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002199.4(IRF2):c.-7+521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,988 control chromosomes in the GnomAD database, including 3,151 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3148 hom., cov: 30)

Exomes 𝑓: 0.27 ( 3 hom. )

Consequence

IRF2
NM_002199.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.135

Publications

3 publications found

Variant links:

Genes affected

IRF2 (HGNC:6117): (interferon regulatory factor 2) IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of histone H4. [provided by RefSeq, Jul 2008]

IRF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4 link	c.-7+521G>A		intron_variant	Intron 1 of 8	ENST00000393593.8	NP_002190.2	P14316-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8 link	c.-7+521G>A		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3		P14316-1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27886

AN:

151826

Hom.:

3143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0625

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.150

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.171

GnomAD4 exome

AF:

0.273

AC:

AN:

Hom.:

AF XY:

0.367

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.263

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.184

AC:

27890

AN:

151944

Hom.:

3148

Cov.:

AF XY:

0.186

AC XY:

13821

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.0624

AC:

2589

AN:

41502

American (AMR)

AF:

0.211

AC:

3226

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

714

AN:

3472

East Asian (EAS)

AF:

0.102

AC:

527

AN:

5144

South Asian (SAS)

AF:

0.323

AC:

1550

AN:

4806

European-Finnish (FIN)

AF:

0.267

AC:

2815

AN:

10556

Middle Eastern (MID)

AF:

0.140

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.233

AC:

15846

AN:

67880

Other (OTH)

AF:

0.170

AC:

358

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1065

2130

3196

4261

5326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.116

Hom.:

228

Bravo

AF:

0.169

Asia WGS

AF:

0.182

AC:

631

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

0.14

PromoterAI

0.044

Neutral

(source)

RBP_binding_hub_radar

0.77

RBP_regulation_power_radar

2.0

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over