6-394293-G-T

Position:

• chr6-394293-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002460.4(IRF4):​c.217-528G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 152,214 control chromosomes in the GnomAD database, including 293 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 0.051 (293 hom., cov: 33)
• Consequence: IRF4 NM_002460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF4	NM_002460.4	c.217-528G>T		intron_variant		ENST00000380956.9	NP_002451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF4	ENST00000380956.9	c.217-528G>T		intron_variant		1	NM_002460.4	ENSP00000370343.4

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7686 AN: 152096 Hom.: 295 Cov.: 33

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0286

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0379

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

GnomAD4 genome AF: 0.0505 AC: 7690 AN: 152214 Hom.: 293 Cov.: 33 AF XY: 0.0533 AC XY: 3969 AN XY: 74424

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.0815

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0286

Gnomad4 NFE AF: 0.0293

Gnomad4 OTH AF: 0.0380

Alfa AF: 0.0329 Hom.: 206

Bravo AF: 0.0536

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs2797307; hg19: chr6-394293;