6-394293-G-T

Variant names:

• chr6-394293-G-T
• rs2797307
• NM_002460.4:c.217-528G>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.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
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IRF4	NM_002460.4	c.217-528G>T		intron_variant	Intron 2 of 8	ENST00000380956.9	NP_002451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF4	ENST00000380956.9	c.217-528G>T		intron_variant	Intron 2 of 8	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

African (AFR) AF: 0.0661 AC: 2746 AN: 41512

American (AMR) AF: 0.0815 AC: 1247 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.120 AC: 620 AN: 5180

South Asian (SAS) AF: 0.130 AC: 628 AN: 4818

European-Finnish (FIN) AF: 0.0286 AC: 303 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0293 AC: 1994 AN: 68022

Other (OTH) AF: 0.0380 AC: 80 AN: 2108

Alfa AF: 0.0359 Hom.: 307

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
PhyloP100		-0.25
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: rs2797307; hg19: chr6-394293;