Genetic Variant IRF4:c.745+144T>G (chr6-399079-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002460.4(IRF4):c.745+144T>G variant causes a intron 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 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.51

Publications

12 publications found

Variant links:

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]

IRF4 links:

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ACMG classification

Classification was made for transcript

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=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF4	NM_002460.4 link	c.745+144T>G		intron_variant	Intron 6 of 8	ENST00000380956.9	NP_002451.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
IRF4	ENST00000380956.9 link	c.745+144T>G	intron_variant	Intron 6 of 8	1	NM_002460.4	ENSP00000370343.4
IRF4	ENST00000696871.1 link	c.742+144T>G	intron_variant	Intron 6 of 8			ENSP00000512940.1
IRF4	ENST00000696873.1 link	c.310+144T>G	intron_variant	Intron 5 of 5			ENSP00000512942.1
IRF4	ENST00000493114.2 link	n.742+144T>G	intron_variant	Intron 6 of 9	5		ENSP00000436094.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

317392

Hom.:

AF XY:

0.00

AC XY:

AN XY:

163254

African (AFR)

AF:

0.00

AC:

AN:

10850

American (AMR)

AF:

0.00

AC:

AN:

14788

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10576

East Asian (EAS)

AF:

0.00

AC:

AN:

28000

South Asian (SAS)

AF:

0.00

AC:

AN:

14616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1466

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

194206

Other (OTH)

AF:

0.00

AC:

AN:

19408

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.19

(source)

DANN

Benign

0.43

PhyloP100

-2.5

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over