Genetic Variant IRF2:c.-7+423C>A (chr4-184473956-G-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+423C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,112 control chromosomes in the GnomAD database, including 9,563 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 0.33 ( 9540 hom., cov: 30)

Exomes 𝑓: 0.36 ( 23 hom. )

Consequence

IRF2
NM_002199.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.167

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:

Genome browser will be placed here

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=-0.62).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4 link	c.-7+423C>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+423C>A		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3		P14316-1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49513

AN:

151662

Hom.:

9532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.318

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.363

GnomAD4 exome

AF:

0.358

AC:

119

AN:

332

Hom.:

Cov.:

AF XY:

0.359

AC XY:

AN XY:

234

show subpopulations

African (AFR)

AF:

0.0833

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.300

AC:

AN:

South Asian (SAS)

AF:

0.367

AC:

AN:

European-Finnish (FIN)

AF:

0.417

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.387

AC:

AN:

238

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.326

AC:

49533

AN:

151780

Hom.:

9540

Cov.:

AF XY:

0.329

AC XY:

24416

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.115

AC:

4743

AN:

41398

American (AMR)

AF:

0.449

AC:

6850

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1326

AN:

3466

East Asian (EAS)

AF:

0.483

AC:

2485

AN:

5150

South Asian (SAS)

AF:

0.353

AC:

1694

AN:

4804

European-Finnish (FIN)

AF:

0.402

AC:

4226

AN:

10516

Middle Eastern (MID)

AF:

0.329

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.399

AC:

27055

AN:

67880

Other (OTH)

AF:

0.361

AC:

759

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1566

3132

4699

6265

7831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

490

980

1470

1960

2450

<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:

0.348

Hom.:

1334

Bravo

AF:

0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.17

PromoterAI

-0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Computational scores

Splicing

Publications

Other links and lift over