6-392866-A-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.-55-232A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 151,882 control chromosomes in the GnomAD database, including 1,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1746 hom., cov: 32)
• Consequence: IRF4 NM_002460.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

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=-0.84).
• BP6: Variant 6-392866-A-G is Benign according to our data. Variant chr6-392866-A-G is described in ClinVar as [Benign]. Clinvar id is 1278447.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF4	NM_002460.4	c.-55-232A>G		intron_variant		ENST00000380956.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF4	ENST00000380956.9	c.-55-232A>G		intron_variant		1	NM_002460.4	P4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19055 AN: 151764 Hom.: 1730 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.126 AC: 19118 AN: 151882 Hom.: 1746 Cov.: 32 AF XY: 0.126 AC XY: 9353 AN XY: 74270

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0589

Gnomad4 NFE AF: 0.0580

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0951 Hom.: 112

Bravo AF: 0.136

Asia WGS AF: 0.189 AC: 655 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.6
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs79324228; hg19: chr6-392866;