rs1877176

Variant names:

• chr6-410513-A-G
• rs1877176
• NM_002460.4:c.*2915A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-410513-A-G
• chr6-410513-A-T

Variant summary

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

The NM_002460.4(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 NM_002460.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 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.*2915A>G		3_prime_UTR	Exon 9 of 9	NP_002451.2	Q15306-1
	IRF4	NM_001195286.2		c.*2915A>G		3_prime_UTR	Exon 9 of 9	NP_001182215.1	Q15306-2
	IRF4	NR_046000.3		n.4515A>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.*2915A>G		3_prime_UTR	Exon 9 of 9	ENSP00000370343.4	Q15306-1
	IRF4	ENST00000866553.1		c.*2915A>G		3_prime_UTR	Exon 8 of 8	ENSP00000536612.1

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

African (AFR) AF: 0.735 AC: 2656 AN: 3614

American (AMR) AF: 0.818 AC: 1918 AN: 2346

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 3735 AN: 4774

East Asian (EAS) AF: 0.857 AC: 9414 AN: 10988

South Asian (SAS) AF: 0.772 AC: 500 AN: 648

European-Finnish (FIN) AF: 0.741 AC: 40 AN: 54

Middle Eastern (MID) AF: 0.766 AC: 363 AN: 474

European-Non Finnish (NFE) AF: 0.799 AC: 37497 AN: 46930

Other (OTH) AF: 0.789 AC: 5022 AN: 6364

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

African (AFR) AF: 0.738 AC: 30638 AN: 41494

American (AMR) AF: 0.827 AC: 12639 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2715 AN: 3470

East Asian (EAS) AF: 0.843 AC: 4370 AN: 5182

South Asian (SAS) AF: 0.796 AC: 3835 AN: 4820

European-Finnish (FIN) AF: 0.856 AC: 9054 AN: 10582

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54205 AN: 67988

Other (OTH) AF: 0.768 AC: 1621 AN: 2112

Alfa AF: 0.794 Hom.: 28815

Bravo AF: 0.781

Asia WGS AF: 0.825 AC: 2871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.66
PhyloP100		-1.2
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: rs1877176; hg19: chr6-410513;