dbSNP rs807684: IRF2: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:

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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4 link	c.-6-83A>G		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.-6-83A>G		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3		P14316-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over