4-184429153-T-G

Variant names:

• chr4-184429153-T-G
• rs807684
• NM_002199.4:c.-6-83A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002199.4(IRF2):​c.-6-83A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 783,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.-6-83A>C		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.-6-83A>C		intron	N/A	ENSP00000377218.3
	IRF2	ENST00000505067.6	TSL:3	c.-6-83A>C		intron	N/A	ENSP00000421927.2
	IRF2	ENST00000504340.2	TSL:4	c.-6-83A>C		intron	N/A	ENSP00000512878.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000128 AC: 1 AN: 783150 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 405506

African (AFR) AF: 0.00 AC: 0 AN: 19736

American (AMR) AF: 0.00 AC: 0 AN: 34866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19984

East Asian (EAS) AF: 0.00 AC: 0 AN: 31904

South Asian (SAS) AF: 0.00 AC: 0 AN: 68552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3610

European-Non Finnish (NFE) AF: 0.00000190 AC: 1 AN: 527034

Other (OTH) AF: 0.00 AC: 0 AN: 36632

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.61
DANN	Benign	0.80
PhyloP100		-1.4

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: rs807684; hg19: chr4-185350307;