6-410513-A-T

Variant names:

• chr6-410513-A-T
• rs1877176
• NM_002460.4:c.*2915A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002460.4(IRF4):​c.*2915A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRF4 NM_002460.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 11 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.*2915A>T		3_prime_UTR	Exon 9 of 9	NP_002451.2
	IRF4	NR_046000.3		n.4515A>T		non_coding_transcript_exon	Exon 10 of 10
	IRF4	NM_001195286.2		c.*2915A>T		3_prime_UTR	Exon 9 of 9	NP_001182215.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF4	ENST00000380956.9	TSL:1 MANE Select	c.*2915A>T		3_prime_UTR	Exon 9 of 9	ENSP00000370343.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 76334 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 35294

African (AFR) AF: 0.00 AC: 0 AN: 3622

American (AMR) AF: 0.00 AC: 0 AN: 2348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4786

East Asian (EAS) AF: 0.00 AC: 0 AN: 10992

South Asian (SAS) AF: 0.00 AC: 0 AN: 648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 54

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 474

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 47038

Other (OTH) AF: 0.00 AC: 0 AN: 6372

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 28815

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.73
PhyloP100		-1.2

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: rs1877176; hg19: chr6-410513;