rs6900384

Variant names:

• chr6-397937-T-G
• rs6900384
• NM_002460.4:c.637+685T>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.637+685T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 152,304 control chromosomes in the GnomAD database, including 581 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 0.084 (581 hom., cov: 33)
• Consequence: IRF4 NM_002460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 14 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF4	NM_002460.4	c.637+685T>G		intron_variant	Intron 5 of 8	ENST00000380956.9	NP_002451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF4	ENST00000380956.9	c.637+685T>G		intron_variant	Intron 5 of 8	1	NM_002460.4	ENSP00000370343.4
IRF4	ENST00000696871.1	c.634+685T>G		intron_variant	Intron 5 of 8			ENSP00000512940.1
IRF4	ENST00000696873.1	c.202+685T>G		intron_variant	Intron 4 of 5			ENSP00000512942.1
IRF4	ENST00000493114.2	n.634+685T>G		intron_variant	Intron 5 of 9	5		ENSP00000436094.2

Frequencies

GnomAD3 genomes AF: 0.0836 AC: 12729 AN: 152186 Hom.: 571 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.0389

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.0619

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0927

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

GnomAD4 genome AF: 0.0838 AC: 12766 AN: 152304 Hom.: 581 Cov.: 33 AF XY: 0.0817 AC XY: 6087 AN XY: 74470

African (AFR) AF: 0.120 AC: 4967 AN: 41550

American (AMR) AF: 0.0696 AC: 1066 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3472

East Asian (EAS) AF: 0.0390 AC: 202 AN: 5186

South Asian (SAS) AF: 0.0417 AC: 201 AN: 4820

European-Finnish (FIN) AF: 0.0619 AC: 657 AN: 10610

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0736 AC: 5010 AN: 68036

Other (OTH) AF: 0.0918 AC: 194 AN: 2114

Alfa AF: 0.0752 Hom.: 194

Bravo AF: 0.0868

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.2
DANN	Benign	0.59
PhyloP100		0.021
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: rs6900384; hg19: chr6-397937;