Genetic Variant NM_002199.4:c.-6-83A>G (chr4-184429153-T-C) – 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.-6-83A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 934,108 control chromosomes in the GnomAD database, including 33,885 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 0.27 ( 5615 hom., cov: 32)

Exomes 𝑓: 0.25 ( 28270 hom. )

Consequence

IRF2
NM_002199.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.44

Publications

9 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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.33 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.-6-83A>G		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.-6-83A>G	intron	N/A	ENSP00000377218.3	P14316-1
IRF2	ENST00000505067.6	TSL:3	c.-6-83A>G	intron	N/A	ENSP00000421927.2	K4DIA4
IRF2	ENST00000883917.1		c.-6-83A>G	intron	N/A	ENSP00000553976.1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40355

AN:

151972

Hom.:

5614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.414

Gnomad NFE

AF:

0.288

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.245

AC:

191698

AN:

782018

Hom.:

28270

AF XY:

0.244

AC XY:

98794

AN XY:

404900

show subpopulations

African (AFR)

AF:

0.220

AC:

4343

AN:

19706

American (AMR)

AF:

0.344

AC:

11965

AN:

34830

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

5692

AN:

19952

East Asian (EAS)

AF:

0.113

AC:

3593

AN:

31872

South Asian (SAS)

AF:

0.195

AC:

13332

AN:

68520

European-Finnish (FIN)

AF:

0.170

AC:

6935

AN:

40780

Middle Eastern (MID)

AF:

0.381

AC:

1372

AN:

3604

European-Non Finnish (NFE)

AF:

0.257

AC:

135199

AN:

526182

Other (OTH)

AF:

0.253

AC:

9267

AN:

36572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

6764

13528

20292

27056

33820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2820

5640

8460

11280

14100

<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:

0.265

AC:

40376

AN:

152090

Hom.:

5615

Cov.:

AF XY:

0.259

AC XY:

19281

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.246

AC:

10217

AN:

41466

American (AMR)

AF:

0.338

AC:

5165

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1041

AN:

3470

East Asian (EAS)

AF:

0.132

AC:

680

AN:

5148

South Asian (SAS)

AF:

0.189

AC:

911

AN:

4830

European-Finnish (FIN)

AF:

0.163

AC:

1723

AN:

10594

Middle Eastern (MID)

AF:

0.418

AC:

122

AN:

292

European-Non Finnish (NFE)

AF:

0.288

AC:

19580

AN:

67978

Other (OTH)

AF:

0.308

AC:

651

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1507

3014

4520

6027

7534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.265

Hom.:

681

Bravo

AF:

0.280

Asia WGS

AF:

0.155

AC:

542

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.76

(source)

DANN

Benign

0.78

PhyloP100

-1.4

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