4-184393259-G-C

Variant names:

• chr4-184393259-G-C
• rs793777
• NM_002199.4:c.695-2510C>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.695-2510C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,054 control chromosomes in the GnomAD database, including 10,581 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 0.37 (10581 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 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.695-2510C>G		intron	N/A	NP_002190.2	P14316-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	ENST00000393593.8	TSL:1 MANE Select	c.695-2510C>G		intron	N/A	ENSP00000377218.3	P14316-1
	IRF2	ENST00000505067.6	TSL:3	c.800-2510C>G		intron	N/A	ENSP00000421927.2	K4DIA4
	IRF2	ENST00000883917.1		c.800-2510C>G		intron	N/A	ENSP00000553976.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56175 AN: 151936 Hom.: 10569 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.370 AC: 56224 AN: 152054 Hom.: 10581 Cov.: 32 AF XY: 0.367 AC XY: 27259 AN XY: 74308

African (AFR) AF: 0.399 AC: 16553 AN: 41470

American (AMR) AF: 0.323 AC: 4943 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1286 AN: 3466

East Asian (EAS) AF: 0.294 AC: 1523 AN: 5174

South Asian (SAS) AF: 0.248 AC: 1194 AN: 4824

European-Finnish (FIN) AF: 0.389 AC: 4108 AN: 10562

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.373 AC: 25361 AN: 67968

Other (OTH) AF: 0.334 AC: 702 AN: 2104

Alfa AF: 0.256 Hom.: 673

Bravo AF: 0.367

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.1
DANN	Benign	0.53
PhyloP100		-0.086
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: rs793777; hg19: chr4-185314413;