rs1473037

chr6-399079-T-Achr6-399079-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002460.4(IRF4):c.745+144T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 469,018 control chromosomes in the GnomAD database, including 142,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (39508 hom., cov: 32)
  • Exomes 𝑓: 0.79 (102657 hom.)
• Consequence: IRF4 NM_002460.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.51

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-399079-T-A is Benign according to our data. Variant chr6-399079-T-A is described in ClinVar as [Benign]. Clinvar id is 1268521.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF4	NM_002460.4	c.745+144T>A		intron_variant		ENST00000380956.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF4	ENST00000380956.9	c.745+144T>A		intron_variant		1	NM_002460.4	P4
IRF4	ENST00000696871.1	c.742+144T>A		intron_variant				A1
IRF4	ENST00000696873.1	c.310+144T>A		intron_variant
IRF4	ENST00000493114.2	c.742+144T>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103152 AN: 151982 Hom.: 39521 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.686

GnomAD4 exome AF: 0.790 AC: 250372 AN: 316918 Hom.: 102657 AF XY: 0.794 AC XY: 129415 AN XY: 162998

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.713

Gnomad4 ASJ exome AF: 0.851

Gnomad4 EAS exome AF: 0.484

Gnomad4 SAS exome AF: 0.704

Gnomad4 FIN exome AF: 0.861

Gnomad4 NFE exome AF: 0.864

Gnomad4 OTH exome AF: 0.765

GnomAD4 genome AF: 0.678 AC: 103134 AN: 152100 Hom.: 39508 Cov.: 32 AF XY: 0.676 AC XY: 50289 AN XY: 74348

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.868

Gnomad4 OTH AF: 0.684

Alfa AF: 0.768 Hom.: 6040

Bravo AF: 0.649

Asia WGS AF: 0.568 AC: 1976 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.19
Dann	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs1473037; hg19: chr6-399079; COSMIC: COSV66705161; COSMIC: COSV66705161;