rs807684

Positions:

• chr4-184429153-T-C

Variant summary

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

The NM_002199.4(IRF2):​c.-6-83A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 934,108 control chromosomes in the GnomAD database, including 33,885 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 0.27 (5615 hom., cov: 32)
  • Exomes 𝑓: 0.25 (28270 hom.)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF2	NM_002199.4	c.-6-83A>G		intron_variant		ENST00000393593.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF2	ENST00000393593.8	c.-6-83A>G		intron_variant		1	NM_002199.4	P1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40355 AN: 151972 Hom.: 5614 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.245 AC: 191698 AN: 782018 Hom.: 28270 AF XY: 0.244 AC XY: 98794 AN XY: 404900

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.265 AC: 40376 AN: 152090 Hom.: 5615 Cov.: 32 AF XY: 0.259 AC XY: 19281 AN XY: 74364

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.308

Alfa AF: 0.265 Hom.: 681

Bravo AF: 0.280

Asia WGS AF: 0.155 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.76
DANN	Benign	0.78

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: rs807684; hg19: chr4-185350307;