6-405900-A-G

Position:

• chr6-405900-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002460.4(IRF4):​c.1212+770A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,148 control chromosomes in the GnomAD database, including 46,275 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 0.78 (46275 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF4	NM_002460.4	c.1212+770A>G		intron_variant		ENST00000380956.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF4	ENST00000380956.9	c.1212+770A>G		intron_variant		1	NM_002460.4	P4
IRF4	ENST00000696871.1	c.1209+770A>G		intron_variant				A1
IRF4	ENST00000493114.2	c.1209+770A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118366 AN: 152030 Hom.: 46227 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.779 AC: 118474 AN: 152148 Hom.: 46275 Cov.: 32 AF XY: 0.774 AC XY: 57566 AN XY: 74384

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.786

Alfa AF: 0.816 Hom.: 70569

Bravo AF: 0.777

Asia WGS AF: 0.754 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.050
DANN	Benign	0.62

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: rs3800262; hg19: chr6-405900;