rs12203592

Variant names:

• chr6-396321-C-T
• rs12203592
• NM_002460.4:c.492+386C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-396321-C-T
• chr6-396321-C-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.492+386C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,306 control chromosomes in the GnomAD database, including 1,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

• Frequency: Genomes: 𝑓 0.10 (1331 hom., cov: 33)
• Consequence: IRF4 NM_002460.4 intron
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 0.112
• Publications: 345 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=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 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.492+386C>T		intron	N/A	NP_002451.2	Q15306-1
	IRF4	NM_001195286.2		c.492+386C>T		intron	N/A	NP_001182215.1	Q15306-2
	IRF4	NR_046000.3		n.605+386C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF4	ENST00000380956.9	TSL:1 MANE Select	c.492+386C>T		intron	N/A	ENSP00000370343.4	Q15306-1
	IRF4	ENST00000866554.1		c.492+386C>T		intron	N/A	ENSP00000536613.1
	IRF4	ENST00000696871.1		c.492+386C>T		intron	N/A	ENSP00000512940.1	Q15306-2

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15281 AN: 152188 Hom.: 1332 Cov.: 33

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0780

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.0260

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.0855

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.100 AC: 15277 AN: 152306 Hom.: 1331 Cov.: 33 AF XY: 0.0889 AC XY: 6625 AN XY: 74494

African (AFR) AF: 0.0328 AC: 1362 AN: 41552

American (AMR) AF: 0.0779 AC: 1192 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 734 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5194

South Asian (SAS) AF: 0.00973 AC: 47 AN: 4828

European-Finnish (FIN) AF: 0.0260 AC: 276 AN: 10626

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11449 AN: 68012

Other (OTH) AF: 0.0846 AC: 179 AN: 2116

Alfa AF: 0.135 Hom.: 6687

Bravo AF: 0.105

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

ClinVar submissions

Significance: Affects

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Skin/hair/eye pigmentation, variation in, 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.74
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs12203592; hg19: chr6-396321;