chr4-184395743-C-T

Position:

• chr4-184395743-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002199.4(IRF2):​c.694+3172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 152,320 control chromosomes in the GnomAD database, including 422 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 0.069 (422 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF2	NM_002199.4	c.694+3172G>A		intron_variant		ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.694+3172G>A		intron_variant		1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10517 AN: 152202 Hom.: 421 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.0469

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.0841

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

GnomAD4 genome AF: 0.0691 AC: 10525 AN: 152320 Hom.: 422 Cov.: 32 AF XY: 0.0673 AC XY: 5010 AN XY: 74484

Gnomad4 AFR AF: 0.0405

Gnomad4 AMR AF: 0.0778

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0681

Gnomad4 FIN AF: 0.0469

Gnomad4 NFE AF: 0.0912

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0895 Hom.: 836

Bravo AF: 0.0698

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.093
DANN	Benign	0.51

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: rs965225; hg19: chr4-185316897;