rs6827018

Variant names:

• chr4-184423452-A-G
• rs6827018
• NM_002199.4:c.88-3884T>C

Variant summary

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

The NM_002199.4(IRF2):​c.88-3884T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,134 control chromosomes in the GnomAD database, including 1,195 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 0.12 (1195 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.176 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.88-3884T>C		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.88-3884T>C		intron	N/A	ENSP00000377218.3	P14316-1
	IRF2	ENST00000505067.6	TSL:3	c.88-3884T>C		intron	N/A	ENSP00000421927.2	K4DIA4
	IRF2	ENST00000883917.1		c.88-3884T>C		intron	N/A	ENSP00000553976.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17998 AN: 152016 Hom.: 1194 Cov.: 32

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.0861

Gnomad ASJ AF: 0.0932

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.118 AC: 18008 AN: 152134 Hom.: 1195 Cov.: 32 AF XY: 0.117 AC XY: 8724 AN XY: 74376

African (AFR) AF: 0.0785 AC: 3257 AN: 41506

American (AMR) AF: 0.0860 AC: 1315 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0932 AC: 323 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.186 AC: 899 AN: 4824

European-Finnish (FIN) AF: 0.142 AC: 1505 AN: 10570

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10148 AN: 67976

Other (OTH) AF: 0.115 AC: 243 AN: 2114

Alfa AF: 0.132 Hom.: 2111

Bravo AF: 0.108

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.035
DANN	Benign	0.21
PhyloP100		-3.4
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: rs6827018; hg19: chr4-185344606;