rs793814

Variant names:

• chr4-184433820-T-A
• rs793814
• NM_002199.4:c.-6-4750A>T

Variant summary

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

The NM_002199.4(IRF2):​c.-6-4750A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,114 control chromosomes in the GnomAD database, including 38,093 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 0.70 (38093 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-6-4750A>T		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.-6-4750A>T		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106881 AN: 151996 Hom.: 38035 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.703 AC: 107001 AN: 152114 Hom.: 38093 Cov.: 32 AF XY: 0.707 AC XY: 52557 AN XY: 74352

African (AFR) AF: 0.766 AC: 31790 AN: 41498

American (AMR) AF: 0.744 AC: 11382 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2245 AN: 3468

East Asian (EAS) AF: 0.961 AC: 4975 AN: 5178

South Asian (SAS) AF: 0.709 AC: 3416 AN: 4816

European-Finnish (FIN) AF: 0.676 AC: 7146 AN: 10564

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43797 AN: 67980

Other (OTH) AF: 0.690 AC: 1458 AN: 2112

Alfa AF: 0.669 Hom.: 4286

Bravo AF: 0.714

Asia WGS AF: 0.822 AC: 2860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.9
DANN	Benign	0.51
PhyloP100		-0.036
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs793814; hg19: chr4-185354974;