rs6812958

Positions:

• chr4-184404088-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393593.8(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 ENST00000393593.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF2	NM_002199.4	c.529+4070C>T		intron_variant		ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.529+4070C>T		intron_variant		1	NM_002199.4	ENSP00000377218	P1

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

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.259

Alfa AF: 0.276 Hom.: 9631

Bravo AF: 0.242

Asia WGS AF: 0.352 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs6812958; hg19: chr4-185325242;