4-184442675-T-G

Variant summary

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

The NM_002199.4(IRF2):c.-6-13605A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 151,764 control chromosomes in the GnomAD database, including 186 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 0.043 (186 hom., cov: 28)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF2	NM_002199.4	c.-6-13605A>C		intron_variant		ENST00000393593.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF2	ENST00000393593.8	c.-6-13605A>C		intron_variant		1	NM_002199.4	P1

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6569 AN: 151646 Hom.: 186 Cov.: 28

Gnomad AFR AF: 0.0728

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.0230

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.00627

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0500

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

GnomAD4 genome AF: 0.0433 AC: 6564 AN: 151764 Hom.: 186 Cov.: 28 AF XY: 0.0414 AC XY: 3071 AN XY: 74136

Gnomad4 AFR AF: 0.0726

Gnomad4 AMR AF: 0.0407

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.0231

Gnomad4 SAS AF: 0.0335

Gnomad4 FIN AF: 0.00627

Gnomad4 NFE AF: 0.0352

Gnomad4 OTH AF: 0.0495

Alfa AF: 0.000609 Hom.: 38371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.25
Dann	Benign	0.24

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: rs7657540; hg19: chr4-185363829;