rs1050975

chr6-408012-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002460.4(IRF4):c.*414G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 292,132 control chromosomes in the GnomAD database, including 103,203 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 0.76 (47563 hom., cov: 32)
  • Exomes 𝑓: 0.89 (55640 hom.)
• Consequence: IRF4 NM_002460.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.974

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF4	NM_002460.4	c.*414G>A		3_prime_UTR_variant	9/9	ENST00000380956.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF4	ENST00000380956.9	c.*414G>A		3_prime_UTR_variant	9/9	1	NM_002460.4	P4
IRF4	ENST00000696871.1			downstream_gene_variant				A1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115847 AN: 152030 Hom.: 47566 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.797

GnomAD4 exome AF: 0.886 AC: 124065 AN: 139984 Hom.: 55640 Cov.: 0 AF XY: 0.893 AC XY: 60227 AN XY: 67438

Gnomad4 AFR exome AF: 0.431

Gnomad4 AMR exome AF: 0.852

Gnomad4 ASJ exome AF: 0.923

Gnomad4 EAS exome AF: 0.786

Gnomad4 SAS exome AF: 0.950

Gnomad4 FIN exome AF: 0.880

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 0.862

GnomAD4 genome AF: 0.762 AC: 115878 AN: 152148 Hom.: 47563 Cov.: 32 AF XY: 0.763 AC XY: 56788 AN XY: 74408

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.928

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.924

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.914

Gnomad4 OTH AF: 0.794

Alfa AF: 0.870 Hom.: 32502

Bravo AF: 0.743

Asia WGS AF: 0.770 AC: 2681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.11
Dann	Benign	0.35

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

Other links and lift over

dbSNP: rs1050975; hg19: chr6-408012;