chr6-408833-G-C

Variant names:

• chr6-408833-G-C
• rs12211228
• NM_002460.4:c.*1235G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002460.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF4	NM_002460.4	MANE Select	c.*1235G>C		3_prime_UTR	Exon 9 of 9	NP_002451.2
	IRF4	NR_046000.3		n.2835G>C		non_coding_transcript_exon	Exon 10 of 10
	IRF4	NM_001195286.2		c.*1235G>C		3_prime_UTR	Exon 9 of 9	NP_001182215.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF4	ENST00000380956.9	TSL:1 MANE Select	c.*1235G>C		3_prime_UTR	Exon 9 of 9	ENSP00000370343.4

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

African (AFR) AF: 0.0744 AC: 283 AN: 3806

American (AMR) AF: 0.112 AC: 277 AN: 2472

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 776 AN: 5042

East Asian (EAS) AF: 0.106 AC: 1236 AN: 11648

South Asian (SAS) AF: 0.193 AC: 135 AN: 700

European-Finnish (FIN) AF: 0.0909 AC: 36 AN: 396

Middle Eastern (MID) AF: 0.137 AC: 67 AN: 490

European-Non Finnish (NFE) AF: 0.137 AC: 6870 AN: 50120

Other (OTH) AF: 0.129 AC: 868 AN: 6708

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

African (AFR) AF: 0.0749 AC: 3110 AN: 41518

American (AMR) AF: 0.103 AC: 1570 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3468

East Asian (EAS) AF: 0.118 AC: 612 AN: 5182

South Asian (SAS) AF: 0.174 AC: 839 AN: 4828

European-Finnish (FIN) AF: 0.0961 AC: 1019 AN: 10606

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9565 AN: 68006

Other (OTH) AF: 0.122 AC: 257 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.54
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12211228; hg19: chr6-408833;