Genetic Variant IRF4:c.*481C>T (chr6-408079-C-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_002460.4(IRF4):c.*481C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 243,320 control chromosomes in the GnomAD database, including 23,837 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 ( 13031 hom., cov: 33)

Exomes 𝑓: 0.47 ( 10806 hom. )

Consequence

IRF4
NM_002460.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.504

Publications

38 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:

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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF4	NM_002460.4 link	c.*481C>T		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.*481C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_002460.4	ENSP00000370343.4		Q15306-1
IRF4	ENST00000696871.1 link	c.*481C>T		downstream_gene_variant				ENSP00000512940.1		Q15306-2

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56734

AN:

151974

Hom.:

13033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0936

Gnomad AMI

AF:

0.400

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.397

GnomAD4 exome

AF:

0.473

AC:

43123

AN:

91228

Hom.:

10806

Cov.:

AF XY:

0.476

AC XY:

20182

AN XY:

42358

show subpopulations

African (AFR)

AF:

0.102

AC:

398

AN:

3910

American (AMR)

AF:

0.459

AC:

1275

AN:

2780

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

2878

AN:

5272

East Asian (EAS)

AF:

0.336

AC:

3866

AN:

11518

South Asian (SAS)

AF:

0.445

AC:

684

AN:

1536

European-Finnish (FIN)

AF:

0.440

AC:

442

AN:

1004

Middle Eastern (MID)

AF:

0.461

AC:

246

AN:

534

European-Non Finnish (NFE)

AF:

0.520

AC:

29733

AN:

57208

Other (OTH)

AF:

0.482

AC:

3601

AN:

7466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1100

2200

3300

4400

5500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

56737

AN:

152092

Hom.:

13031

Cov.:

AF XY:

0.372

AC XY:

27646

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0933

AC:

3874

AN:

41512

American (AMR)

AF:

0.446

AC:

6813

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

1911

AN:

3470

East Asian (EAS)

AF:

0.313

AC:

1618

AN:

5172

South Asian (SAS)

AF:

0.426

AC:

2054

AN:

4824

European-Finnish (FIN)

AF:

0.476

AC:

5023

AN:

10562

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.502

AC:

34101

AN:

67970

Other (OTH)

AF:

0.400

AC:

843

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1622

3244

4866

6488

8110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.463

Hom.:

23620

Bravo

AF:

0.359

Asia WGS

AF:

0.353

AC:

1228

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.1

(source)

DANN

Benign

0.35

PhyloP100

0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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