rs3733475

Variant names:

• chr4-184473956-G-T
• rs3733475
• NM_002199.4:c.-7+423C>A

Variant summary

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

The NM_002199.4(IRF2):​c.-7+423C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,112 control chromosomes in the GnomAD database, including 9,563 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 0.33 (9540 hom., cov: 30)
  • Exomes 𝑓: 0.36 (23 hom.)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-7+423C>A		intron_variant	Intron 1 of 8	ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.-7+423C>A		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49513 AN: 151662 Hom.: 9532 Cov.: 30

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.358 AC: 119 AN: 332 Hom.: 23 Cov.: 0 AF XY: 0.359 AC XY: 84 AN XY: 234

Gnomad4 AFR exome AF: 0.0833

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.326 AC: 49533 AN: 151780 Hom.: 9540 Cov.: 30 AF XY: 0.329 AC XY: 24416 AN XY: 74160

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.361

Alfa AF: 0.357 Hom.: 1329

Bravo AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3733475; hg19: chr4-185395110;