6-405900-A-G

Variant names:

• chr6-405900-A-G
• rs3800262
• NM_002460.4:c.1212+770A>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.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
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 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.1212+770A>G		intron	N/A	NP_002451.2
	IRF4	NM_001195286.2		c.1209+770A>G		intron	N/A	NP_001182215.1
	IRF4	NR_046000.3		n.1322+770A>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.1212+770A>G		intron	N/A	ENSP00000370343.4
	IRF4	ENST00000696871.1		c.1209+770A>G		intron	N/A	ENSP00000512940.1
	IRF4	ENST00000493114.2	TSL:5	n.1209+770A>G		intron	N/A	ENSP00000436094.2

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

African (AFR) AF: 0.709 AC: 29402 AN: 41494

American (AMR) AF: 0.782 AC: 11945 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2940 AN: 3470

East Asian (EAS) AF: 0.704 AC: 3646 AN: 5176

South Asian (SAS) AF: 0.725 AC: 3489 AN: 4814

European-Finnish (FIN) AF: 0.788 AC: 8352 AN: 10598

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56030 AN: 67998

Other (OTH) AF: 0.786 AC: 1659 AN: 2112

Alfa AF: 0.813 Hom.: 100339

Bravo AF: 0.777

Asia WGS AF: 0.754 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.050
DANN	Benign	0.62
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: rs3800262; hg19: chr6-405900;