4-184442675-T-C

Variant names:

• chr4-184442675-T-C
• rs7657540
• NM_002199.4:c.-6-13605A>G

Variant summary

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

The NM_002199.4(IRF2):​c.-6-13605A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 151,658 control chromosomes in the GnomAD database, including 35,181 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 0.67 (35181 hom., cov: 28)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• Publications: 4 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	NM_002199.4	MANE Select	c.-6-13605A>G		intron	N/A	NP_002190.2	P14316-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	ENST00000393593.8	TSL:1 MANE Select	c.-6-13605A>G		intron	N/A	ENSP00000377218.3	P14316-1
	IRF2	ENST00000505067.6	TSL:3	c.-6-13605A>G		intron	N/A	ENSP00000421927.2	K4DIA4
	IRF2	ENST00000883917.1		c.-6-13605A>G		intron	N/A	ENSP00000553976.1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102188 AN: 151540 Hom.: 35155 Cov.: 28

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.674 AC: 102253 AN: 151658 Hom.: 35181 Cov.: 28 AF XY: 0.673 AC XY: 49850 AN XY: 74080

African (AFR) AF: 0.546 AC: 22551 AN: 41270

American (AMR) AF: 0.654 AC: 9947 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2382 AN: 3470

East Asian (EAS) AF: 0.626 AC: 3231 AN: 5158

South Asian (SAS) AF: 0.729 AC: 3496 AN: 4794

European-Finnish (FIN) AF: 0.758 AC: 7968 AN: 10508

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50488 AN: 67932

Other (OTH) AF: 0.660 AC: 1388 AN: 2102

Alfa AF: 0.749 Hom.: 50430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.24
PhyloP100		-0.86
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: rs7657540; hg19: chr4-185363829;