6-398775-G-C

Variant names:

• chr6-398775-G-C
• rs2671422
• NM_002460.4:c.638-53G>C

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.638-53G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000837 in 1,195,380 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: IRF4 NM_002460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 0 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=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF4	NM_002460.4	c.638-53G>C		intron_variant	Intron 5 of 8	ENST00000380956.9	NP_002451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF4	ENST00000380956.9	c.638-53G>C		intron_variant	Intron 5 of 8	1	NM_002460.4	ENSP00000370343.4
IRF4	ENST00000696871.1	c.635-53G>C		intron_variant	Intron 5 of 8			ENSP00000512940.1
IRF4	ENST00000696873.1	c.203-53G>C		intron_variant	Intron 4 of 5			ENSP00000512942.1
IRF4	ENST00000493114.2	n.635-53G>C		intron_variant	Intron 5 of 9	5		ENSP00000436094.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.37e-7 AC: 1 AN: 1195380 Hom.: 0 AF XY: 0.00000167 AC XY: 1 AN XY: 598130

African (AFR) AF: 0.00 AC: 0 AN: 27984

American (AMR) AF: 0.00 AC: 0 AN: 40928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22948

East Asian (EAS) AF: 0.0000268 AC: 1 AN: 37284

South Asian (SAS) AF: 0.00 AC: 0 AN: 75616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4824

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 884404

Other (OTH) AF: 0.00 AC: 0 AN: 50550

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0090
DANN	Benign	0.40
PhyloP100		-2.3

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: rs2671422; hg19: chr6-398775;