rs872071

Variant names:

• chr6-411064-A-G
• rs872071
• NM_002460.4:c.*3466A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-411064-A-G
• chr6-411064-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.*3466A>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 0.408 in 233,212 control chromosomes in the GnomAD database, including 22,658 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 (12998 hom., cov: 33)
  • Exomes 𝑓: 0.47 (9660 hom.)
• Consequence: IRF4 NM_002460.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 101 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=-0.86).
• 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.*3466A>G		3_prime_UTR	Exon 9 of 9	NP_002451.2	Q15306-1
	IRF4	NM_001195286.2		c.*3466A>G		3_prime_UTR	Exon 9 of 9	NP_001182215.1	Q15306-2
	IRF4	NR_046000.3		n.5066A>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.*3466A>G		3_prime_UTR	Exon 9 of 9	ENSP00000370343.4	Q15306-1
	IRF4	ENST00000866553.1		c.*3466A>G		3_prime_UTR	Exon 8 of 8	ENSP00000536612.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56715 AN: 151968 Hom.: 13002 Cov.: 33

Gnomad AFR AF: 0.0938

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.473 AC: 38337 AN: 81126 Hom.: 9660 Cov.: 0 AF XY: 0.477 AC XY: 17821 AN XY: 37372

African (AFR) AF: 0.101 AC: 390 AN: 3858

American (AMR) AF: 0.457 AC: 1131 AN: 2476

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 2714 AN: 5086

East Asian (EAS) AF: 0.333 AC: 3851 AN: 11578

South Asian (SAS) AF: 0.441 AC: 309 AN: 700

European-Finnish (FIN) AF: 0.500 AC: 82 AN: 164

Middle Eastern (MID) AF: 0.471 AC: 231 AN: 490

European-Non Finnish (NFE) AF: 0.527 AC: 26365 AN: 50018

Other (OTH) AF: 0.483 AC: 3264 AN: 6756

GnomAD4 genome AF: 0.373 AC: 56716 AN: 152086 Hom.: 12998 Cov.: 33 AF XY: 0.372 AC XY: 27639 AN XY: 74328

African (AFR) AF: 0.0935 AC: 3882 AN: 41510

American (AMR) AF: 0.447 AC: 6833 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1878 AN: 3472

East Asian (EAS) AF: 0.313 AC: 1612 AN: 5158

South Asian (SAS) AF: 0.418 AC: 2016 AN: 4828

European-Finnish (FIN) AF: 0.477 AC: 5042 AN: 10572

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34114 AN: 67958

Other (OTH) AF: 0.398 AC: 839 AN: 2106

Alfa AF: 0.462 Hom.: 79773

Bravo AF: 0.359

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.62
PhyloP100		0.076
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: rs872071; hg19: chr6-411064;