Variant rs2671422 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002460.4(IRF4):c.638-53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,345,942 control chromosomes in the GnomAD database, including 22,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4668 hom., cov: 33)

Exomes 𝑓: 0.14 ( 17439 hom. )

Consequence

IRF4
NM_002460.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-398775-G-A is Benign according to our data. Variant chr6-398775-G-A is described in ClinVar as [Benign]. Clinvar id is 1273865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF4	NM_002460.4 linkuse as main transcript	c.638-53G>A		intron_variant		ENST00000380956.9	NP_002451.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
IRF4	ENST00000380956.9 linkuse as main transcript	c.638-53G>A	intron_variant	1	NM_002460.4	ENSP00000370343	P4	Q15306-1
IRF4	ENST00000696871.1 linkuse as main transcript	c.635-53G>A	intron_variant			ENSP00000512940	A1	Q15306-2
IRF4	ENST00000696873.1 linkuse as main transcript	c.203-53G>A	intron_variant			ENSP00000512942
IRF4	ENST00000493114.2 linkuse as main transcript	c.635-53G>A	intron_variant, NMD_transcript_variant	5		ENSP00000436094

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32363

AN:

152046

Hom.:

4631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.516

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.145

AC:

172771

AN:

1193778

Hom.:

17439

AF XY:

0.146

AC XY:

87451

AN XY:

597336

show subpopulations

Gnomad4 AFR exome

AF:

0.350

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.513

Gnomad4 SAS exome

AF:

0.253

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.213

AC:

32467

AN:

152164

Hom.:

4668

Cov.:

AF XY:

0.217

AC XY:

16149

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.350

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.517

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.225

Alfa

AF:

0.137

Hom.:

3532

Bravo

AF:

0.228

Asia WGS

AF:

0.406

AC:

1410

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

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

-0.83

CADD

Benign

0.023

DANN

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over