rs12512614

Variant names:

• chr4-184399962-G-T
• rs12512614
• NM_002199.4:c.530-883C>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.530-883C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,146 control chromosomes in the GnomAD database, including 4,410 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 0.24 (4410 hom., cov: 33)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 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.530-883C>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.530-883C>A		intron	N/A	ENSP00000377218.3	P14316-1
	IRF2	ENST00000505067.6	TSL:3	c.635-883C>A		intron	N/A	ENSP00000421927.2	K4DIA4
	IRF2	ENST00000883917.1		c.635-883C>A		intron	N/A	ENSP00000553976.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36214 AN: 152028 Hom.: 4407 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.238 AC: 36232 AN: 152146 Hom.: 4410 Cov.: 33 AF XY: 0.237 AC XY: 17653 AN XY: 74378

African (AFR) AF: 0.245 AC: 10170 AN: 41500

American (AMR) AF: 0.213 AC: 3255 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 905 AN: 3462

East Asian (EAS) AF: 0.263 AC: 1364 AN: 5188

South Asian (SAS) AF: 0.199 AC: 958 AN: 4820

European-Finnish (FIN) AF: 0.253 AC: 2679 AN: 10588

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16135 AN: 67992

Other (OTH) AF: 0.218 AC: 460 AN: 2112

Alfa AF: 0.238 Hom.: 3213

Bravo AF: 0.236

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.55
DANN	Benign	0.39
PhyloP100		-0.42
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: rs12512614; hg19: chr4-185321116;