Genetic Variant NM_002460.4: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

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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