rs6900384

Positions:

• chr6-397937-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• 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/exons	MANE	Protein	UniProt
IRF4	NM_002460.4	c.637+685T>G		intron_variant		ENST00000380956.9	NP_002451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF4	ENST00000380956.9	c.637+685T>G		intron_variant		1	NM_002460.4	ENSP00000370343.4
IRF4	ENST00000696871.1	c.634+685T>G		intron_variant				ENSP00000512940.1
IRF4	ENST00000696873.1	c.202+685T>G		intron_variant				ENSP00000512942.1
IRF4	ENST00000493114.2	n.634+685T>G		intron_variant		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

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0696

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.0390

Gnomad4 SAS AF: 0.0417

Gnomad4 FIN AF: 0.0619

Gnomad4 NFE AF: 0.0736

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0727 Hom.: 159

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

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: rs6900384; hg19: chr6-397937;