rs3733473

Variant names:

• chr4-184429268-A-G
• rs3733473
• NM_002199.4:c.-6-198T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-184429268-A-G
• chr4-184429268-A-T

Variant summary

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

The ENST00000393593.8(IRF2):​c.-6-198T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,098 control chromosomes in the GnomAD database, including 47,681 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 0.79 (47681 hom., cov: 32)
• Consequence: IRF2 ENST00000393593.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393593.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	NM_002199.4	MANE Select	c.-6-198T>C		intron	N/A	NP_002190.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	ENST00000393593.8	TSL:1 MANE Select	c.-6-198T>C		intron	N/A	ENSP00000377218.3
	IRF2	ENST00000505067.6	TSL:3	c.-6-198T>C		intron	N/A	ENSP00000421927.2
	IRF2	ENST00000504340.2	TSL:4	c.-6-198T>C		intron	N/A	ENSP00000512878.1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120010 AN: 151980 Hom.: 47640 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.790 AC: 120107 AN: 152098 Hom.: 47681 Cov.: 32 AF XY: 0.785 AC XY: 58376 AN XY: 74356

African (AFR) AF: 0.823 AC: 34162 AN: 41498

American (AMR) AF: 0.808 AC: 12356 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2548 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2690 AN: 5158

South Asian (SAS) AF: 0.718 AC: 3467 AN: 4826

European-Finnish (FIN) AF: 0.745 AC: 7872 AN: 10560

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54308 AN: 67966

Other (OTH) AF: 0.779 AC: 1646 AN: 2114

Alfa AF: 0.790 Hom.: 26924

Bravo AF: 0.796

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.64
PhyloP100		-0.16
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: rs3733473; hg19: chr4-185350422;