NM_002199.4:c.-7+13950G>A

Variant names:

• chr4-184460429-C-T
• rs793801
• NM_002199.4:c.-7+13950G>A

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+13950G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,010 control chromosomes in the GnomAD database, including 14,644 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 0.43 (14644 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 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.-7+13950G>A		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.-7+13950G>A		intron	N/A	ENSP00000377218.3	P14316-1
	IRF2	ENST00000505067.6	TSL:3	c.-7+13540G>A		intron	N/A	ENSP00000421927.2	K4DIA4
	IRF2	ENST00000883917.1		c.-7+13950G>A		intron	N/A	ENSP00000553976.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65939 AN: 151892 Hom.: 14628 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.434 AC: 65981 AN: 152010 Hom.: 14644 Cov.: 32 AF XY: 0.435 AC XY: 32289 AN XY: 74294

African (AFR) AF: 0.523 AC: 21677 AN: 41442

American (AMR) AF: 0.388 AC: 5924 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1747 AN: 3468

East Asian (EAS) AF: 0.352 AC: 1821 AN: 5180

South Asian (SAS) AF: 0.451 AC: 2173 AN: 4814

European-Finnish (FIN) AF: 0.413 AC: 4363 AN: 10568

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26697 AN: 67944

Other (OTH) AF: 0.431 AC: 906 AN: 2104

Alfa AF: 0.461 Hom.: 8588

Bravo AF: 0.435

Asia WGS AF: 0.418 AC: 1454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.69
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs793801; hg19: chr4-185381583;