4-184438124-C-T

Variant names:

• chr4-184438124-C-T
• rs11723606
• NM_002199.4:c.-6-9054G>A

Variant summary

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

The NM_002199.4(IRF2):​c.-6-9054G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,116 control chromosomes in the GnomAD database, including 2,664 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 0.17 (2664 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-6-9054G>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.-6-9054G>A		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25959 AN: 151998 Hom.: 2666 Cov.: 32

Gnomad AFR AF: 0.0775

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0302

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.171 AC: 25947 AN: 152116 Hom.: 2664 Cov.: 32 AF XY: 0.169 AC XY: 12572 AN XY: 74352

Gnomad4 AFR AF: 0.0774

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0304

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.177

Alfa AF: 0.204 Hom.: 3423

Bravo AF: 0.161

Asia WGS AF: 0.108 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.45

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: rs11723606; hg19: chr4-185359278;