NM_002460.4:c.1100-1219A>G

Variant names:

• chr6-403799-A-G
• rs3778607
• NM_002460.4:c.1100-1219A>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.1100-1219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,016 control chromosomes in the GnomAD database, including 15,088 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 0.43 (15088 hom., cov: 32)
• Consequence: IRF4 NM_002460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 23 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF4	NM_002460.4	MANE Select	c.1100-1219A>G		intron	N/A	NP_002451.2
	IRF4	NM_001195286.2		c.1097-1219A>G		intron	N/A	NP_001182215.1
	IRF4	NR_046000.3		n.1210-1219A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF4	ENST00000380956.9	TSL:1 MANE Select	c.1100-1219A>G		intron	N/A	ENSP00000370343.4
	IRF4	ENST00000696871.1		c.1097-1219A>G		intron	N/A	ENSP00000512940.1
	IRF4	ENST00000493114.2	TSL:5	n.1097-1219A>G		intron	N/A	ENSP00000436094.2

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64970 AN: 151898 Hom.: 15084 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.428 AC: 64994 AN: 152016 Hom.: 15088 Cov.: 32 AF XY: 0.425 AC XY: 31584 AN XY: 74314

African (AFR) AF: 0.247 AC: 10245 AN: 41464

American (AMR) AF: 0.474 AC: 7235 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2113 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1379 AN: 5182

South Asian (SAS) AF: 0.422 AC: 2032 AN: 4814

European-Finnish (FIN) AF: 0.461 AC: 4872 AN: 10570

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35580 AN: 67930

Other (OTH) AF: 0.450 AC: 948 AN: 2108

Alfa AF: 0.493 Hom.: 40545

Bravo AF: 0.422

Asia WGS AF: 0.350 AC: 1217 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.31
PhyloP100		-1.4
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: rs3778607; hg19: chr6-403799;