4-184404088-G-A

Variant names:

• chr4-184404088-G-A
• rs6812958
• NM_002199.4:c.529+4070C>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.529+4070C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,116 control chromosomes in the GnomAD database, including 5,244 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 0.24 (5244 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 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.529+4070C>T		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.529+4070C>T		intron	N/A	ENSP00000377218.3
	IRF2	ENST00000505067.6	TSL:3	c.634+3091C>T		intron	N/A	ENSP00000421927.2
	IRF2	ENST00000504340.2	TSL:4	c.529+4070C>T		intron	N/A	ENSP00000512878.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37203 AN: 151998 Hom.: 5243 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.245 AC: 37207 AN: 152116 Hom.: 5244 Cov.: 32 AF XY: 0.251 AC XY: 18674 AN XY: 74342

African (AFR) AF: 0.106 AC: 4387 AN: 41522

American (AMR) AF: 0.333 AC: 5094 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 928 AN: 3472

East Asian (EAS) AF: 0.353 AC: 1828 AN: 5178

South Asian (SAS) AF: 0.360 AC: 1729 AN: 4806

European-Finnish (FIN) AF: 0.317 AC: 3341 AN: 10554

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19111 AN: 67994

Other (OTH) AF: 0.259 AC: 547 AN: 2108

Alfa AF: 0.270 Hom.: 22928

Bravo AF: 0.242

Asia WGS AF: 0.352 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.51
PhyloP100		-0.030
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: rs6812958; hg19: chr4-185325242;