6-392783-G-A

Position:

• chr6-392783-G-A

Variant summary

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

The ENST00000380956.9(IRF4):​c.-55-315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 152,278 control chromosomes in the GnomAD database, including 1,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.089 (1055 hom., cov: 33)
• Consequence: IRF4 ENST00000380956.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.499

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=-0.86).
• BP6: Variant 6-392783-G-A is Benign according to our data. Variant chr6-392783-G-A is described in ClinVar as [Benign]. Clinvar id is 1272812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF4	NM_002460.4	c.-55-315G>A		intron_variant		ENST00000380956.9	NP_002451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF4	ENST00000380956.9	c.-55-315G>A		intron_variant		1	NM_002460.4	ENSP00000370343	P4

Frequencies

GnomAD3 genomes AF: 0.0883 AC: 13440 AN: 152160 Hom.: 1042 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0988

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0886 AC: 13493 AN: 152278 Hom.: 1055 Cov.: 33 AF XY: 0.0889 AC XY: 6617 AN XY: 74458

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.0998

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.0907

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0630 Hom.: 117

Bravo AF: 0.0987

Asia WGS AF: 0.181 AC: 626 AN: 3476

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	-0.86
CADD	Benign	3.6
DANN	Benign	0.93

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: rs9501998; hg19: chr6-392783;