rs12504466

Positions:

• chr4-184432645-T-C

Variant summary

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

The NM_002199.4(IRF2):​c.-6-3575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,048 control chromosomes in the GnomAD database, including 14,498 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 0.43 (14498 hom., cov: 33)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.777

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF2	NM_002199.4	c.-6-3575A>G		intron_variant		ENST00000393593.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF2	ENST00000393593.8	c.-6-3575A>G		intron_variant		1	NM_002199.4	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64622 AN: 151930 Hom.: 14476 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.425 AC: 64680 AN: 152048 Hom.: 14498 Cov.: 33 AF XY: 0.429 AC XY: 31861 AN XY: 74304

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.430

Alfa AF: 0.473 Hom.: 35117

Bravo AF: 0.408

Asia WGS AF: 0.551 AC: 1915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.9
DANN	Benign	0.40

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: rs12504466; hg19: chr4-185353799;