4-184473858-C-T

Position:

• chr4-184473858-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393593.8(IRF2):​c.-7+521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,988 control chromosomes in the GnomAD database, including 3,151 homozygotes. 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: 𝑓 0.18 (3148 hom., cov: 30)
  • Exomes 𝑓: 0.27 (3 hom.)
• Consequence: IRF2 ENST00000393593.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

Genes affected

IRF2 (HGNC:6117): (interferon regulatory factor 2) IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of histone H4. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-7+521G>A		intron_variant		ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.-7+521G>A		intron_variant		1	NM_002199.4	ENSP00000377218	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27886 AN: 151826 Hom.: 3143 Cov.: 30

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.273 AC: 12 AN: 44 Hom.: 3 AF XY: 0.367 AC XY: 11 AN XY: 30

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.263

GnomAD4 genome AF: 0.184 AC: 27890 AN: 151944 Hom.: 3148 Cov.: 30 AF XY: 0.186 AC XY: 13821 AN XY: 74266

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.170

Alfa AF: 0.118 Hom.: 224

Bravo AF: 0.169

Asia WGS AF: 0.182 AC: 631 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Uncertain	0.98
RBP_binding_hub_radar		0.77
RBP_regulation_power_radar		2.0

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: rs66801661; hg19: chr4-185395012;