chr4-184429650-G-C

Variant names:

• chr4-184429650-G-C
• rs3756093
• NM_002199.4:c.-6-580C>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.-6-580C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,138 control chromosomes in the GnomAD database, including 48,643 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 0.80 (48643 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-6-580C>G		intron_variant	Intron 1 of 8	ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.-6-580C>G		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.796 AC: 121021 AN: 152020 Hom.: 48612 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.796 AC: 121110 AN: 152138 Hom.: 48643 Cov.: 32 AF XY: 0.792 AC XY: 58913 AN XY: 74366

African (AFR) AF: 0.699 AC: 28974 AN: 41476

American (AMR) AF: 0.835 AC: 12781 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2715 AN: 3470

East Asian (EAS) AF: 0.683 AC: 3531 AN: 5168

South Asian (SAS) AF: 0.747 AC: 3595 AN: 4814

European-Finnish (FIN) AF: 0.802 AC: 8483 AN: 10580

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58288 AN: 68016

Other (OTH) AF: 0.790 AC: 1666 AN: 2110

Alfa AF: 0.827 Hom.: 6481

Bravo AF: 0.797

Asia WGS AF: 0.717 AC: 2495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.21
DANN	Benign	0.45
PhyloP100		-2.0
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: rs3756093; hg19: chr4-185350804;