chr4-184435742-T-C

Variant names:

• chr4-184435742-T-C
• rs793810
• NM_002199.4:c.-6-6672A>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.-6-6672A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,130 control chromosomes in the GnomAD database, including 62,889 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 0.91 (62889 hom., cov: 29)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	NM_002199.4	MANE Select	c.-6-6672A>G		intron	N/A	NP_002190.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	ENST00000393593.8	TSL:1 MANE Select	c.-6-6672A>G		intron	N/A	ENSP00000377218.3
	IRF2	ENST00000505067.6	TSL:3	c.-6-6672A>G		intron	N/A	ENSP00000421927.2
	IRF2	ENST00000504340.2	TSL:4	c.-6-6672A>G		intron	N/A	ENSP00000512878.1

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138080 AN: 152012 Hom.: 62827 Cov.: 29

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.895

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

GnomAD4 genome AF: 0.908 AC: 138200 AN: 152130 Hom.: 62889 Cov.: 29 AF XY: 0.911 AC XY: 67718 AN XY: 74370

African (AFR) AF: 0.859 AC: 35625 AN: 41468

American (AMR) AF: 0.924 AC: 14135 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3010 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5163 AN: 5166

South Asian (SAS) AF: 0.967 AC: 4657 AN: 4814

European-Finnish (FIN) AF: 0.952 AC: 10089 AN: 10602

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62613 AN: 67992

Other (OTH) AF: 0.896 AC: 1894 AN: 2114

Alfa AF: 0.918 Hom.: 42852

Bravo AF: 0.903

Asia WGS AF: 0.972 AC: 3380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.78
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: rs793810; hg19: chr4-185356896;