Genetic Variant IRF2:c.-6-19842C>T (chr4-184448912-G-A) – 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.-6-19842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,014 control chromosomes in the GnomAD database, including 20,061 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 0.47 ( 20053 hom., cov: 32)

Exomes 𝑓: 0.60 ( 8 hom. )

Consequence

IRF2
NM_002199.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.125

Publications

6 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	NM_002199.4	MANE Select	c.-6-19842C>T		intron	N/A	NP_002190.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IRF2	ENST00000393593.8	TSL:1 MANE Select	c.-6-19842C>T	intron	N/A	ENSP00000377218.3
IRF2	ENST00000504340.2	TSL:4	c.-1242C>T	5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	ENSP00000512878.1
IRF2	ENST00000504340.2	TSL:4	c.-1242C>T	5_prime_UTR	Exon 2 of 10	ENSP00000512878.1

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71620

AN:

151866

Hom.:

20044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.621

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.640

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.550

GnomAD4 exome

AF:

0.600

AC:

AN:

Hom.:

Cov.:

AF XY:

0.636

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.714

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.471

AC:

71636

AN:

151984

Hom.:

20053

Cov.:

AF XY:

0.473

AC XY:

35156

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.156

AC:

6471

AN:

41466

American (AMR)

AF:

0.597

AC:

9115

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.640

AC:

2223

AN:

3472

East Asian (EAS)

AF:

0.382

AC:

1973

AN:

5170

South Asian (SAS)

AF:

0.517

AC:

2490

AN:

4812

European-Finnish (FIN)

AF:

0.580

AC:

6104

AN:

10532

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.609

AC:

41373

AN:

67964

Other (OTH)

AF:

0.545

AC:

1145

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1642

3285

4927

6570

8212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

628

1256

1884

2512

3140

<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:

0.571

Hom.:

110063

Bravo

AF:

0.462

Asia WGS

AF:

0.432

AC:

1505

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.6

(source)

DANN

Benign

0.71

PhyloP100

-0.13

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over