6-405873-T-C

Variant names:

• chr6-405873-T-C
• rs17825664
• NM_002460.4:c.1212+743T>C

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+743T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 152,294 control chromosomes in the GnomAD database, including 216 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 0.051 (216 hom., cov: 33)
• Consequence: IRF4 NM_002460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0593 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF4	NM_002460.4	MANE Select	c.1212+743T>C		intron	N/A	NP_002451.2
	IRF4	NM_001195286.2		c.1209+743T>C		intron	N/A	NP_001182215.1
	IRF4	NR_046000.3		n.1322+743T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF4	ENST00000380956.9	TSL:1 MANE Select	c.1212+743T>C		intron	N/A	ENSP00000370343.4
	IRF4	ENST00000866554.1		c.1212+743T>C		intron	N/A	ENSP00000536613.1
	IRF4	ENST00000696871.1		c.1209+743T>C		intron	N/A	ENSP00000512940.1

Frequencies

GnomAD3 genomes AF: 0.0506 AC: 7700 AN: 152176 Hom.: 216 Cov.: 33

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.0495

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0506 AC: 7699 AN: 152294 Hom.: 216 Cov.: 33 AF XY: 0.0492 AC XY: 3662 AN XY: 74462

African (AFR) AF: 0.0368 AC: 1529 AN: 41564

American (AMR) AF: 0.0485 AC: 743 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3468

East Asian (EAS) AF: 0.0160 AC: 83 AN: 5188

South Asian (SAS) AF: 0.0299 AC: 144 AN: 4822

European-Finnish (FIN) AF: 0.0495 AC: 525 AN: 10606

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0608 AC: 4136 AN: 68020

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

Alfa AF: 0.0604 Hom.: 528

Bravo AF: 0.0515

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	15
DANN	Benign	0.64
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: rs17825664; hg19: chr6-405873;