dbSNP rs872071: IRF4:c.*3466A>G (chr6-411064-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002460.4(IRF4):c.*3466A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 233,212 control chromosomes in the GnomAD database, including 22,658 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 0.37 ( 12998 hom., cov: 33)

Exomes 𝑓: 0.47 ( 9660 hom. )

Consequence

IRF4
NM_002460.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0760

Publications

101 publications found

Variant links:

Genes affected

IRF4 (HGNC:6119): (interferon regulatory factor 4) The protein encoded by this gene belongs to the IRF (interferon regulatory factor) family of transcription factors, characterized by an unique tryptophan pentad repeat DNA-binding domain. The IRFs are important in the regulation of interferons in response to infection by virus, and in the regulation of interferon-inducible genes. This family member is lymphocyte specific and negatively regulates Toll-like-receptor (TLR) signaling that is central to the activation of innate and adaptive immune systems. A chromosomal translocation involving this gene and the IgH locus, t(6;14)(p25;q32), may be a cause of multiple myeloma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2010]

IRF4 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 = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF4	NM_002460.4 link	c.*3466A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000380956.9	NP_002451.2	Q15306-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF4	ENST00000380956.9 link	c.*3466A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_002460.4	ENSP00000370343.4		Q15306-1

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56715

AN:

151968

Hom.:

13002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0938

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.395

GnomAD4 exome

AF:

0.473

AC:

38337

AN:

81126

Hom.:

9660

Cov.:

AF XY:

0.477

AC XY:

17821

AN XY:

37372

show subpopulations

African (AFR)

AF:

0.101

AC:

390

AN:

3858

American (AMR)

AF:

0.457

AC:

1131

AN:

2476

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

2714

AN:

5086

East Asian (EAS)

AF:

0.333

AC:

3851

AN:

11578

South Asian (SAS)

AF:

0.441

AC:

309

AN:

700

European-Finnish (FIN)

AF:

0.500

AC:

AN:

164

Middle Eastern (MID)

AF:

0.471

AC:

231

AN:

490

European-Non Finnish (NFE)

AF:

0.527

AC:

26365

AN:

50018

Other (OTH)

AF:

0.483

AC:

3264

AN:

6756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

960

1920

2880

3840

4800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.373

AC:

56716

AN:

152086

Hom.:

12998

Cov.:

AF XY:

0.372

AC XY:

27639

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0935

AC:

3882

AN:

41510

American (AMR)

AF:

0.447

AC:

6833

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

1878

AN:

3472

East Asian (EAS)

AF:

0.313

AC:

1612

AN:

5158

South Asian (SAS)

AF:

0.418

AC:

2016

AN:

4828

European-Finnish (FIN)

AF:

0.477

AC:

5042

AN:

10572

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.502

AC:

34114

AN:

67958

Other (OTH)

AF:

0.398

AC:

839

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1636

3272

4907

6543

8179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.462

Hom.:

79773

Bravo

AF:

0.359

Asia WGS

AF:

0.350

AC:

1217

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.0

(source)

DANN

Benign

0.62

PhyloP100

0.076

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