rs9391997

Variant names:

• chr6-409119-A-G
• rs9391997
• NM_002460.4:c.*1521A>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.*1521A>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 0.413 in 213,584 control chromosomes in the GnomAD database, including 20,754 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 0.39 (13321 hom., cov: 32)
  • Exomes 𝑓: 0.48 (7433 hom.)
• Consequence: IRF4 NM_002460.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797
• Publications: 28 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=-0.84).
• 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.*1521A>G		3_prime_UTR	Exon 9 of 9	NP_002451.2	Q15306-1
	IRF4	NM_001195286.2		c.*1521A>G		3_prime_UTR	Exon 9 of 9	NP_001182215.1	Q15306-2
	IRF4	NR_046000.3		n.3121A>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.*1521A>G		3_prime_UTR	Exon 9 of 9	ENSP00000370343.4	Q15306-1
	IRF4	ENST00000866553.1		c.*1521A>G		3_prime_UTR	Exon 8 of 8	ENSP00000536612.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58860 AN: 151884 Hom.: 13322 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.477 AC: 29358 AN: 61582 Hom.: 7433 Cov.: 0 AF XY: 0.480 AC XY: 13701 AN XY: 28564

African (AFR) AF: 0.138 AC: 391 AN: 2826

American (AMR) AF: 0.466 AC: 855 AN: 1836

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 2155 AN: 3972

East Asian (EAS) AF: 0.330 AC: 3095 AN: 9370

South Asian (SAS) AF: 0.436 AC: 226 AN: 518

European-Finnish (FIN) AF: 0.500 AC: 20 AN: 40

Middle Eastern (MID) AF: 0.476 AC: 181 AN: 380

European-Non Finnish (NFE) AF: 0.531 AC: 19910 AN: 37466

Other (OTH) AF: 0.488 AC: 2525 AN: 5174

GnomAD4 genome AF: 0.387 AC: 58871 AN: 152002 Hom.: 13321 Cov.: 32 AF XY: 0.386 AC XY: 28681 AN XY: 74302

African (AFR) AF: 0.141 AC: 5838 AN: 41452

American (AMR) AF: 0.452 AC: 6907 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1908 AN: 3464

East Asian (EAS) AF: 0.312 AC: 1613 AN: 5168

South Asian (SAS) AF: 0.426 AC: 2053 AN: 4818

European-Finnish (FIN) AF: 0.476 AC: 5024 AN: 10558

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34168 AN: 67958

Other (OTH) AF: 0.407 AC: 858 AN: 2106

Alfa AF: 0.445 Hom.: 5997

Bravo AF: 0.375

Asia WGS AF: 0.353 AC: 1229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.67
DANN	Benign	0.58
PhyloP100		-0.80
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: rs9391997; hg19: chr6-409119;