rs11132242

Positions:

• chr4-184400787-A-G
• chr4-184400787-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IRF2	NM_002199.4	c.530-1708T>C		intron_variant		ENST00000393593.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF2	ENST00000393593.8	c.530-1708T>C		intron_variant		1	NM_002199.4	P1

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

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.343

Alfa AF: 0.368 Hom.: 13947

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11132242; hg19: chr4-185321941;