4-184390253-C-T

Variant names:

• chr4-184390253-C-T
• rs4862365
• NM_002199.4:c.741+450G>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.741+450G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,220 control chromosomes in the GnomAD database, including 1,075 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 0.11 (1075 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.864
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.741+450G>A		intron_variant	Intron 8 of 8	ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.741+450G>A		intron_variant	Intron 8 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17045 AN: 152102 Hom.: 1077 Cov.: 32

Gnomad AFR AF: 0.0728

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.112 AC: 17044 AN: 152220 Hom.: 1075 Cov.: 32 AF XY: 0.112 AC XY: 8368 AN XY: 74442

African (AFR) AF: 0.0727 AC: 3018 AN: 41536

American (AMR) AF: 0.0779 AC: 1191 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5188

South Asian (SAS) AF: 0.131 AC: 634 AN: 4822

European-Finnish (FIN) AF: 0.170 AC: 1801 AN: 10596

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9467 AN: 68002

Other (OTH) AF: 0.0924 AC: 195 AN: 2110

Alfa AF: 0.115 Hom.: 328

Bravo AF: 0.103

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.77
PhyloP100		-0.86
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: rs4862365; hg19: chr4-185311407;