6-410417-A-G

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Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002460.4(IRF4):​c.*2819A>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 0.406 in 229,098 control chromosomes in the GnomAD database, including 22,159 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 ( 12987 hom., cov: 33)
Exomes 𝑓: 0.47 ( 9172 hom. )

Consequence

IRF4
NM_002460.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.321
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
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/exons MANE Protein UniProt
IRF4NM_002460.4 linkc.*2819A>G 3_prime_UTR_variant 9/9 ENST00000380956.9 NP_002451.2 Q15306-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IRF4ENST00000380956.9 linkc.*2819A>G 3_prime_UTR_variant 9/91 NM_002460.4 ENSP00000370343.4 Q15306-1

Frequencies

GnomAD3 genomes
AF:
0.373
AC:
56703
AN:
152000
Hom.:
12991
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0936
Gnomad AMI
AF:
0.398
Gnomad AMR
AF:
0.447
Gnomad ASJ
AF:
0.541
Gnomad EAS
AF:
0.312
Gnomad SAS
AF:
0.416
Gnomad FIN
AF:
0.476
Gnomad MID
AF:
0.484
Gnomad NFE
AF:
0.502
Gnomad OTH
AF:
0.395
GnomAD4 exome
AF:
0.472
AC:
36336
AN:
76980
Hom.:
9172
Cov.:
0
AF XY:
0.476
AC XY:
16884
AN XY:
35446
show subpopulations
Gnomad4 AFR exome
AF:
0.101
Gnomad4 AMR exome
AF:
0.457
Gnomad4 ASJ exome
AF:
0.534
Gnomad4 EAS exome
AF:
0.330
Gnomad4 SAS exome
AF:
0.444
Gnomad4 FIN exome
AF:
0.464
Gnomad4 NFE exome
AF:
0.527
Gnomad4 OTH exome
AF:
0.486
GnomAD4 genome
AF:
0.373
AC:
56704
AN:
152118
Hom.:
12987
Cov.:
33
AF XY:
0.372
AC XY:
27642
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0933
Gnomad4 AMR
AF:
0.447
Gnomad4 ASJ
AF:
0.541
Gnomad4 EAS
AF:
0.313
Gnomad4 SAS
AF:
0.417
Gnomad4 FIN
AF:
0.476
Gnomad4 NFE
AF:
0.502
Gnomad4 OTH
AF:
0.398
Alfa
AF:
0.449
Hom.:
6427
Bravo
AF:
0.359
Asia WGS
AF:
0.351
AC:
1220
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
4.8
DANN
Benign
0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1050979; hg19: chr6-410417; API