rs1877176

Positions:

• chr6-410513-A-G
• chr6-410513-A-T

Variant summary

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

The ENST00000380956.9(IRF4):​c.*2915A>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 0.793 in 228,338 control chromosomes in the GnomAD database, including 72,069 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 0.79 (47489 hom., cov: 32)
  • Exomes 𝑓: 0.80 (24580 hom.)
• Consequence: IRF4 ENST00000380956.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF4	NM_002460.4	c.*2915A>G		3_prime_UTR_variant	9/9	ENST00000380956.9	NP_002451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF4	ENST00000380956.9	c.*2915A>G		3_prime_UTR_variant	9/9	1	NM_002460.4	ENSP00000370343	P4

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119784 AN: 152028 Hom.: 47445 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.766

GnomAD4 exome AF: 0.803 AC: 61145 AN: 76192 Hom.: 24580 Cov.: 0 AF XY: 0.804 AC XY: 28311 AN XY: 35226

Gnomad4 AFR exome AF: 0.735

Gnomad4 AMR exome AF: 0.818

Gnomad4 ASJ exome AF: 0.782

Gnomad4 EAS exome AF: 0.857

Gnomad4 SAS exome AF: 0.772

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.799

Gnomad4 OTH exome AF: 0.789

GnomAD4 genome AF: 0.788 AC: 119888 AN: 152146 Hom.: 47489 Cov.: 32 AF XY: 0.792 AC XY: 58879 AN XY: 74382

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.827

Gnomad4 ASJ AF: 0.782

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.768

Alfa AF: 0.800 Hom.: 18534

Bravo AF: 0.781

Asia WGS AF: 0.825 AC: 2871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.66

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: rs1877176; hg19: chr6-410513;