dbSNP rs3733475: 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002199.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	NM_002199.4	MANE Select	c.-7+423C>A		intron	N/A	NP_002190.2	P14316-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IRF2	ENST00000393593.8	TSL:1 MANE Select	c.-7+423C>A	intron	N/A	ENSP00000377218.3	P14316-1
IRF2	ENST00000505067.6	TSL:3	c.-7+13C>A	intron	N/A	ENSP00000421927.2	K4DIA4
IRF2	ENST00000883917.1		c.-7+423C>A	intron	N/A	ENSP00000553976.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over