rs1050976

Positions:

• chr6-408079-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

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=-0.81).
• 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/exons	MANE	UniProt
IRF4	NM_002460.4	c.*481C>T		3_prime_UTR_variant	9/9	ENST00000380956.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF4	ENST00000380956.9	c.*481C>T		3_prime_UTR_variant	9/9	1	NM_002460.4	P4

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56734 AN: 151974 Hom.: 13033 Cov.: 33

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.: 0 AF XY: 0.476 AC XY: 20182 AN XY: 42358

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.459

Gnomad4 ASJ exome AF: 0.546

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.520

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.373 AC: 56737 AN: 152092 Hom.: 13031 Cov.: 33 AF XY: 0.372 AC XY: 27646 AN XY: 74344

Gnomad4 AFR AF: 0.0933

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.400

Alfa AF: 0.478 Hom.: 16654

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
DANN	Benign	0.35

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

LitVar

Other links and lift over

dbSNP: rs1050976; hg19: chr6-408079; COSMIC: COSV66706708; COSMIC: COSV66706708;