rs3775582

Variant names:

• chr4-184467333-G-A
• rs3775582
• NM_002199.4:c.-7+7046C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-184467333-G-A
• chr4-184467333-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002199.4(IRF2):​c.-7+7046C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 151,982 control chromosomes in the GnomAD database, including 1,432 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 0.13 (1432 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 9 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-7+7046C>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.-7+7046C>T		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20477 AN: 151864 Hom.: 1426 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.135 AC: 20514 AN: 151982 Hom.: 1432 Cov.: 32 AF XY: 0.134 AC XY: 9981 AN XY: 74272

African (AFR) AF: 0.181 AC: 7503 AN: 41410

American (AMR) AF: 0.113 AC: 1719 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3468

East Asian (EAS) AF: 0.160 AC: 824 AN: 5162

South Asian (SAS) AF: 0.172 AC: 829 AN: 4822

European-Finnish (FIN) AF: 0.0755 AC: 797 AN: 10556

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8093 AN: 67980

Other (OTH) AF: 0.125 AC: 263 AN: 2110

Alfa AF: 0.123 Hom.: 5478

Bravo AF: 0.138

Asia WGS AF: 0.181 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.61
PhyloP100		-0.075
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: rs3775582; hg19: chr4-185388487;