rs793794

Positions:

• chr4-184441883-G-A
• chr4-184441883-G-C

Variant summary

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

The NM_002199.4(IRF2):​c.-6-12813C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,154 control chromosomes in the GnomAD database, including 3,704 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 0.20 (3704 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF2	NM_002199.4	c.-6-12813C>T		intron_variant		ENST00000393593.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF2	ENST00000393593.8	c.-6-12813C>T		intron_variant		1	NM_002199.4	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30262 AN: 152036 Hom.: 3681 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.0889

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.199 AC: 30323 AN: 152154 Hom.: 3704 Cov.: 32 AF XY: 0.192 AC XY: 14318 AN XY: 74386

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0901

Gnomad4 FIN AF: 0.0889

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.214

Alfa AF: 0.168 Hom.: 3192

Bravo AF: 0.212

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.68

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: rs793794; hg19: chr4-185363037;