4-184468922-A-T

Variant names:

• chr4-184468922-A-T
• rs7667268
• NM_002199.4:c.-7+5457T>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+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
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 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+5457T>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+5457T>A		intron	N/A	ENSP00000377218.3
	IRF2	ENST00000505067.6	TSL:3	c.-7+5047T>A		intron	N/A	ENSP00000421927.2
	IRF2	ENST00000504340.2	TSL:4	c.-1381+5457T>A		intron	N/A	ENSP00000512878.1

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

African (AFR) AF: 0.553 AC: 22900 AN: 41428

American (AMR) AF: 0.299 AC: 4565 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1405 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1110 AN: 5178

South Asian (SAS) AF: 0.289 AC: 1391 AN: 4814

European-Finnish (FIN) AF: 0.264 AC: 2792 AN: 10576

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.352 AC: 23925 AN: 67950

Other (OTH) AF: 0.407 AC: 857 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.38
PhyloP100		0.52
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: rs7667268; hg19: chr4-185390076;