rs3775554

Variant names:

• chr4-184409246-G-C
• rs3775554
• NM_002199.4:c.412-971C>G

Variant summary

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

The NM_002199.4(IRF2):​c.412-971C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,102 control chromosomes in the GnomAD database, including 1,657 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 0.14 (1657 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002199.4. 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.412-971C>G		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.412-971C>G		intron	N/A	ENSP00000377218.3
	IRF2	ENST00000505067.6	TSL:3	c.412-971C>G		intron	N/A	ENSP00000421927.2
	IRF2	ENST00000504340.2	TSL:4	c.412-971C>G		intron	N/A	ENSP00000512878.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21777 AN: 151984 Hom.: 1657 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0986

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.143 AC: 21795 AN: 152102 Hom.: 1657 Cov.: 32 AF XY: 0.144 AC XY: 10709 AN XY: 74356

African (AFR) AF: 0.179 AC: 7420 AN: 41464

American (AMR) AF: 0.0987 AC: 1508 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1293 AN: 5158

South Asian (SAS) AF: 0.136 AC: 657 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10584

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8437 AN: 68000

Other (OTH) AF: 0.128 AC: 270 AN: 2108

Alfa AF: 0.140 Hom.: 229

Bravo AF: 0.138

Asia WGS AF: 0.187 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.50
PhyloP100		-0.68
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: rs3775554; hg19: chr4-185330400;