4-184389064-C-T

Position:

• chr4-184389064-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002199.4(IRF2):​c.744G>A​(p.Gly248=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,611,808 control chromosomes in the GnomAD database, including 129,879 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (11585 hom., cov: 32)
  • Exomes 𝑓: 0.40 (118294 hom.)
• Consequence: IRF2 NM_002199.4 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF2	NM_002199.4	c.744G>A	p.Gly248=	splice_region_variant, synonymous_variant	9/9	ENST00000393593.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF2	ENST00000393593.8	c.744G>A	p.Gly248=	splice_region_variant, synonymous_variant	9/9	1	NM_002199.4	P1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58841 AN: 151940 Hom.: 11579 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.410

GnomAD3 exomes AF: 0.427 AC: 106260 AN: 248924 Hom.: 23457 AF XY: 0.426 AC XY: 57398 AN XY: 134752

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.582

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.408

Gnomad SAS exome AF: 0.510

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.386

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.399 AC: 582891 AN: 1459750 Hom.: 118294 Cov.: 34 AF XY: 0.402 AC XY: 291785 AN XY: 726288

Gnomad4 AFR exome AF: 0.340

Gnomad4 AMR exome AF: 0.564

Gnomad4 ASJ exome AF: 0.393

Gnomad4 EAS exome AF: 0.388

Gnomad4 SAS exome AF: 0.511

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.387 AC: 58879 AN: 152058 Hom.: 11585 Cov.: 32 AF XY: 0.390 AC XY: 28977 AN XY: 74348

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.412

Alfa AF: 0.383 Hom.: 10908

Bravo AF: 0.393

Asia WGS AF: 0.492 AC: 1714 AN: 3478

EpiCase AF: 0.380

EpiControl AF: 0.379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.3
DANN	Benign	0.55

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: rs1131553; hg19: chr4-185310218; COSMIC: COSV66928779;