4-184468922-A-T

Variant names:

• chr4-184468922-A-T
• rs7667268
• NM_002199.4:c.-7+5457T>A

Variant summary

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

The NM_002199.4(IRF2):​c.-7+5457T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,000 control chromosomes in the GnomAD database, including 12,564 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 0.39 (12564 hom., cov: 31)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-7+5457T>A		intron_variant	Intron 1 of 8	ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.-7+5457T>A		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59387 AN: 151882 Hom.: 12526 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.391 AC: 59479 AN: 152000 Hom.: 12564 Cov.: 31 AF XY: 0.385 AC XY: 28629 AN XY: 74304

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.407

Alfa AF: 0.154 Hom.: 255

Bravo AF: 0.401

Asia WGS AF: 0.296 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.38

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: rs7667268; hg19: chr4-185390076;