rs809909

Variant names:

• chr4-184403456-T-A
• rs809909
• NM_002199.4:c.530-4377A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002199.4(IRF2):​c.530-4377A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,960 control chromosomes in the GnomAD database, including 28,493 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 0.60 (28493 hom., cov: 31)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.530-4377A>T		intron_variant	Intron 6 of 8	ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.530-4377A>T		intron_variant	Intron 6 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91808 AN: 151842 Hom.: 28494 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.604 AC: 91843 AN: 151960 Hom.: 28493 Cov.: 31 AF XY: 0.606 AC XY: 45041 AN XY: 74300

African (AFR) AF: 0.446 AC: 18461 AN: 41394

American (AMR) AF: 0.662 AC: 10121 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2151 AN: 3464

East Asian (EAS) AF: 0.684 AC: 3540 AN: 5176

South Asian (SAS) AF: 0.717 AC: 3459 AN: 4826

European-Finnish (FIN) AF: 0.640 AC: 6754 AN: 10550

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45245 AN: 67950

Other (OTH) AF: 0.611 AC: 1289 AN: 2110

Alfa AF: 0.641 Hom.: 3919

Bravo AF: 0.600

Asia WGS AF: 0.679 AC: 2362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.62
DANN	Benign	0.72
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs809909; hg19: chr4-185324610;