rs13146124

chr4-184470254-G-Achr4-184470254-G-T

Variant summary

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

The NM_002199.4(IRF2):c.-7+4125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,060 control chromosomes in the GnomAD database, including 3,565 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 0.20 (3565 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF2	NM_002199.4	c.-7+4125C>T		intron_variant		ENST00000393593.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF2	ENST00000393593.8	c.-7+4125C>T		intron_variant		1	NM_002199.4	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30044 AN: 151942 Hom.: 3559 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.198 AC: 30047 AN: 152060 Hom.: 3565 Cov.: 32 AF XY: 0.202 AC XY: 15015 AN XY: 74300

Gnomad4 AFR AF: 0.0696

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.181

Alfa AF: 0.211 Hom.: 506

Bravo AF: 0.180

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.25
Dann	Benign	0.60

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: rs13146124; hg19: chr4-185391408;