chr4-184411876-C-T

Variant names:

• chr4-184411876-C-T
• rs10009261
• NM_002199.4:c.412-3601G>A

Variant summary

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

The NM_002199.4(IRF2):​c.412-3601G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,468 control chromosomes in the GnomAD database, including 7,500 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 (7500 hom., cov: 28)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.412-3601G>A		intron_variant	Intron 5 of 8	ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.412-3601G>A		intron_variant	Intron 5 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43097 AN: 151350 Hom.: 7500 Cov.: 28

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.285 AC: 43107 AN: 151468 Hom.: 7500 Cov.: 28 AF XY: 0.282 AC XY: 20902 AN XY: 74018

African (AFR) AF: 0.0828 AC: 3421 AN: 41334

American (AMR) AF: 0.304 AC: 4618 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1015 AN: 3466

East Asian (EAS) AF: 0.183 AC: 938 AN: 5130

South Asian (SAS) AF: 0.357 AC: 1712 AN: 4800

European-Finnish (FIN) AF: 0.344 AC: 3600 AN: 10460

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26788 AN: 67762

Other (OTH) AF: 0.283 AC: 595 AN: 2100

Alfa AF: 0.349 Hom.: 12916

Bravo AF: 0.275

Asia WGS AF: 0.244 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.063
DANN	Benign	0.52
PhyloP100		-1.2
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: rs10009261; hg19: chr4-185333030;