NM_002199.4:c.530-1708T>C

Variant names:

• chr4-184400787-A-G
• rs11132242
• NM_002199.4:c.530-1708T>C

Variant summary

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

The NM_002199.4(IRF2):​c.530-1708T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,008 control chromosomes in the GnomAD database, including 9,437 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 0.35 (9437 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.530-1708T>C		intron_variant	Intron 6 of 8	ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.530-1708T>C		intron_variant	Intron 6 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53111 AN: 151892 Hom.: 9437 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.350 AC: 53140 AN: 152008 Hom.: 9437 Cov.: 32 AF XY: 0.345 AC XY: 25609 AN XY: 74266

African (AFR) AF: 0.337 AC: 13982 AN: 41446

American (AMR) AF: 0.311 AC: 4755 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1555 AN: 5172

South Asian (SAS) AF: 0.300 AC: 1444 AN: 4806

European-Finnish (FIN) AF: 0.319 AC: 3363 AN: 10546

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25517 AN: 67976

Other (OTH) AF: 0.343 AC: 724 AN: 2110

Alfa AF: 0.363 Hom.: 19752

Bravo AF: 0.350

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.39
PhyloP100		0.10
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: rs11132242; hg19: chr4-185321941;