4-184410823-A-G

Variant names:

• chr4-184410823-A-G
• rs3775556
• NM_002199.4:c.412-2548T>C

Variant summary

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

The NM_002199.4(IRF2):​c.412-2548T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,080 control chromosomes in the GnomAD database, including 6,154 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 0.28 (6154 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738
• Publications: 6 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=-0.47).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.349 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	NM_002199.4	MANE Select	c.412-2548T>C		intron	N/A	NP_002190.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	ENST00000393593.8	TSL:1 MANE Select	c.412-2548T>C		intron	N/A	ENSP00000377218.3
	IRF2	ENST00000505067.6	TSL:3	c.412-2548T>C		intron	N/A	ENSP00000421927.2
	IRF2	ENST00000883917.1		c.412-2548T>C		intron	N/A	ENSP00000553976.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42565 AN: 151962 Hom.: 6153 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.280 AC: 42593 AN: 152080 Hom.: 6154 Cov.: 32 AF XY: 0.280 AC XY: 20805 AN XY: 74342

African (AFR) AF: 0.307 AC: 12723 AN: 41470

American (AMR) AF: 0.357 AC: 5461 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3468

East Asian (EAS) AF: 0.225 AC: 1165 AN: 5174

South Asian (SAS) AF: 0.303 AC: 1460 AN: 4826

European-Finnish (FIN) AF: 0.209 AC: 2208 AN: 10568

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17779 AN: 67970

Other (OTH) AF: 0.289 AC: 610 AN: 2110

Alfa AF: 0.269 Hom.: 24051

Bravo AF: 0.293

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.74
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: rs3775556; hg19: chr4-185331977;