rs62339994

Variant names:

• chr4-184472872-C-T
• rs62339994
• NM_002199.4:c.-7+1507G>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+1507G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,188 control chromosomes in the GnomAD database, including 3,349 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 0.19 (3349 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 3 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	NM_002199.4	MANE Select	c.-7+1507G>A		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.-7+1507G>A		intron	N/A	ENSP00000377218.3
	IRF2	ENST00000505067.6	TSL:3	c.-7+1097G>A		intron	N/A	ENSP00000421927.2
	IRF2	ENST00000504340.2	TSL:4	c.-1381+1507G>A		intron	N/A	ENSP00000512878.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28464 AN: 152070 Hom.: 3343 Cov.: 32

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.187 AC: 28464 AN: 152188 Hom.: 3349 Cov.: 32 AF XY: 0.191 AC XY: 14181 AN XY: 74408

African (AFR) AF: 0.0451 AC: 1876 AN: 41570

American (AMR) AF: 0.215 AC: 3281 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3472

East Asian (EAS) AF: 0.148 AC: 767 AN: 5166

South Asian (SAS) AF: 0.263 AC: 1267 AN: 4822

European-Finnish (FIN) AF: 0.316 AC: 3345 AN: 10598

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16564 AN: 67946

Other (OTH) AF: 0.178 AC: 376 AN: 2116

Alfa AF: 0.214 Hom.: 491

Bravo AF: 0.171

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.87
PhyloP100		0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs62339994; hg19: chr4-185394026;