rs3778607

chr6-403799-A-Gchr6-403799-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF4	NM_002460.4	c.1100-1219A>G		intron_variant		ENST00000380956.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF4	ENST00000380956.9	c.1100-1219A>G		intron_variant		1	NM_002460.4	P4
IRF4	ENST00000696871.1	c.1097-1219A>G		intron_variant				A1
IRF4	ENST00000493114.2	c.1097-1219A>G		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.450

Alfa AF: 0.502 Hom.: 27774

Bravo AF: 0.422

Asia WGS AF: 0.350 AC: 1217 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.6
Dann	Benign	0.31

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: rs3778607; hg19: chr6-403799;