6-410417-A-G

Variant names:

• chr6-410417-A-G
• rs1050979
• NM_002460.4:c.*2819A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002460.4(IRF4):​c.*2819A>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 0.406 in 229,098 control chromosomes in the GnomAD database, including 22,159 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 (12987 hom., cov: 33)
  • Exomes 𝑓: 0.47 (9172 hom.)
• Consequence: IRF4 NM_002460.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 24 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]

IRF4 Gene-Disease associations (from GenCC):

• combined immunodeficiency

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF4	NM_002460.4	MANE Select	c.*2819A>G		3_prime_UTR	Exon 9 of 9	NP_002451.2	Q15306-1
	IRF4	NM_001195286.2		c.*2819A>G		3_prime_UTR	Exon 9 of 9	NP_001182215.1	Q15306-2
	IRF4	NR_046000.3		n.4419A>G		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF4	ENST00000380956.9	TSL:1 MANE Select	c.*2819A>G		3_prime_UTR	Exon 9 of 9	ENSP00000370343.4	Q15306-1
	IRF4	ENST00000866553.1		c.*2819A>G		3_prime_UTR	Exon 8 of 8	ENSP00000536612.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56703 AN: 152000 Hom.: 12991 Cov.: 33

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.472 AC: 36336 AN: 76980 Hom.: 9172 Cov.: 0 AF XY: 0.476 AC XY: 16884 AN XY: 35446

African (AFR) AF: 0.101 AC: 373 AN: 3700

American (AMR) AF: 0.457 AC: 1066 AN: 2332

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 2593 AN: 4856

East Asian (EAS) AF: 0.330 AC: 3652 AN: 11076

South Asian (SAS) AF: 0.444 AC: 294 AN: 662

European-Finnish (FIN) AF: 0.464 AC: 26 AN: 56

Middle Eastern (MID) AF: 0.477 AC: 224 AN: 470

European-Non Finnish (NFE) AF: 0.527 AC: 24977 AN: 47380

Other (OTH) AF: 0.486 AC: 3131 AN: 6448

GnomAD4 genome AF: 0.373 AC: 56704 AN: 152118 Hom.: 12987 Cov.: 33 AF XY: 0.372 AC XY: 27642 AN XY: 74350

African (AFR) AF: 0.0933 AC: 3876 AN: 41524

American (AMR) AF: 0.447 AC: 6829 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1876 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1618 AN: 5176

South Asian (SAS) AF: 0.417 AC: 2007 AN: 4810

European-Finnish (FIN) AF: 0.476 AC: 5030 AN: 10564

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.502 AC: 34135 AN: 67980

Other (OTH) AF: 0.398 AC: 838 AN: 2104

Alfa AF: 0.440 Hom.: 7530

Bravo AF: 0.359

Asia WGS AF: 0.351 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.56
PhyloP100		0.32
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: rs1050979; hg19: chr6-410417;