rs17488073

Positions:

• chr4-184407819-C-G
• chr4-184407819-C-T

Variant summary

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

The NM_002199.4(IRF2):​c.529+339G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,284 control chromosomes in the GnomAD database, including 1,056 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 0.10 (1056 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF2	NM_002199.4	c.529+339G>C		intron_variant		ENST00000393593.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF2	ENST00000393593.8	c.529+339G>C		intron_variant		1	NM_002199.4	P1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15243 AN: 152166 Hom.: 1057 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.000768

Gnomad SAS AF: 0.0480

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.100 AC: 15239 AN: 152284 Hom.: 1056 Cov.: 32 AF XY: 0.0950 AC XY: 7074 AN XY: 74460

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.0925

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0511 Hom.: 37

Bravo AF: 0.0985

Asia WGS AF: 0.0240 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.61

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: rs17488073; hg19: chr4-185328973;