NM_002199.4:c.-6-12813C>T

Variant names:

• chr4-184441883-G-A
• rs793794
• NM_002199.4:c.-6-12813C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002199.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	NM_002199.4	MANE Select	c.-6-12813C>T		intron	N/A	NP_002190.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	ENST00000393593.8	TSL:1 MANE Select	c.-6-12813C>T		intron	N/A	ENSP00000377218.3
	IRF2	ENST00000505067.6	TSL:3	c.-6-12813C>T		intron	N/A	ENSP00000421927.2
	IRF2	ENST00000504340.2	TSL:4	c.-7+5794C>T		intron	N/A	ENSP00000512878.1

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

African (AFR) AF: 0.329 AC: 13658 AN: 41464

American (AMR) AF: 0.161 AC: 2463 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3468

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5186

South Asian (SAS) AF: 0.0901 AC: 435 AN: 4830

European-Finnish (FIN) AF: 0.0889 AC: 942 AN: 10600

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11000 AN: 68010

Other (OTH) AF: 0.214 AC: 452 AN: 2112

Alfa AF: 0.175 Hom.: 4448

Bravo AF: 0.212

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.68
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs793794; hg19: chr4-185363037;