rs12211228

chr6-408833-G-Cchr6-408833-G-T

Variant summary

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

The NM_002460.4(IRF4):c.*1235G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 233,604 control chromosomes in the GnomAD database, including 1,890 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 0.12 (1194 hom., cov: 33)
  • Exomes 𝑓: 0.13 (696 hom.)
• Consequence: IRF4 NM_002460.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF4	NM_002460.4	c.*1235G>C		3_prime_UTR_variant	9/9	ENST00000380956.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF4	ENST00000380956.9	c.*1235G>C		3_prime_UTR_variant	9/9	1	NM_002460.4	P4

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17666 AN: 152104 Hom.: 1196 Cov.: 33

Gnomad AFR AF: 0.0750

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0961

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.130 AC: 10548 AN: 81382 Hom.: 696 Cov.: 0 AF XY: 0.129 AC XY: 4862 AN XY: 37722

Gnomad4 AFR exome AF: 0.0744

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.0909

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.116 AC: 17664 AN: 152222 Hom.: 1194 Cov.: 33 AF XY: 0.115 AC XY: 8571 AN XY: 74422

Gnomad4 AFR AF: 0.0749

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.0961

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0528 Hom.: 50

Bravo AF: 0.115

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.54

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: rs12211228; hg19: chr6-408833;