rs62339994

Positions:

• chr4-184472872-C-T

Variant summary

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

The ENST00000393593.8(IRF2):​c.-7+1507G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,188 control chromosomes in the GnomAD database, including 3,349 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 0.19 (3349 hom., cov: 32)
• Consequence: IRF2 ENST00000393593.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-7+1507G>A		intron_variant		ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.-7+1507G>A		intron_variant		1	NM_002199.4	ENSP00000377218	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28464 AN: 152070 Hom.: 3343 Cov.: 32

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.187 AC: 28464 AN: 152188 Hom.: 3349 Cov.: 32 AF XY: 0.191 AC XY: 14181 AN XY: 74408

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.178

Alfa AF: 0.214 Hom.: 491

Bravo AF: 0.171

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs62339994; hg19: chr4-185394026;