rs13139310

Positions:

• chr4-184435757-G-A
• chr4-184435757-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.-6-6687C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,100 control chromosomes in the GnomAD database, including 2,213 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 0.15 (2213 hom., cov: 31)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-6-6687C>T		intron_variant		ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.-6-6687C>T		intron_variant		1	NM_002199.4	ENSP00000377218	P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23248 AN: 151982 Hom.: 2217 Cov.: 31

Gnomad AFR AF: 0.0484

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0284

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.153 AC: 23231 AN: 152100 Hom.: 2213 Cov.: 31 AF XY: 0.152 AC XY: 11270 AN XY: 74350

Gnomad4 AFR AF: 0.0482

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0284

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.163

Alfa AF: 0.182 Hom.: 1549

Bravo AF: 0.143

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13139310; hg19: chr4-185356911;