NM_002199.4:c.-6-19228C>T

Variant names:

• chr4-184448298-G-A
• rs3775572
• NM_002199.4:c.-6-19228C>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.-6-19228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,136 control chromosomes in the GnomAD database, including 54,839 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 0.82 (54839 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-6-19228C>T		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.-6-19228C>T		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124778 AN: 152018 Hom.: 54821 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.821 AC: 124836 AN: 152136 Hom.: 54839 Cov.: 32 AF XY: 0.825 AC XY: 61412 AN XY: 74402

African (AFR) AF: 0.473 AC: 19576 AN: 41410

American (AMR) AF: 0.927 AC: 14177 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3152 AN: 3472

East Asian (EAS) AF: 0.770 AC: 3979 AN: 5168

South Asian (SAS) AF: 0.917 AC: 4426 AN: 4828

European-Finnish (FIN) AF: 0.988 AC: 10498 AN: 10624

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.971 AC: 66039 AN: 68026

Other (OTH) AF: 0.871 AC: 1837 AN: 2108

Alfa AF: 0.920 Hom.: 252337

Bravo AF: 0.801

Asia WGS AF: 0.797 AC: 2774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		0.054
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: rs3775572; hg19: chr4-185369452;