rs13146124

Variant names:

• chr4-184470254-G-A
• rs13146124
• NM_002199.4:c.-7+4125C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-184470254-G-A
• chr4-184470254-G-T

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+4125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,060 control chromosomes in the GnomAD database, including 3,565 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 0.20 (3565 hom., cov: 32)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-7+4125C>T		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+4125C>T		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30044 AN: 151942 Hom.: 3559 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.198 AC: 30047 AN: 152060 Hom.: 3565 Cov.: 32 AF XY: 0.202 AC XY: 15015 AN XY: 74300

African (AFR) AF: 0.0696 AC: 2891 AN: 41512

American (AMR) AF: 0.217 AC: 3318 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3472

East Asian (EAS) AF: 0.156 AC: 804 AN: 5170

South Asian (SAS) AF: 0.311 AC: 1498 AN: 4818

European-Finnish (FIN) AF: 0.332 AC: 3497 AN: 10546

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16678 AN: 67958

Other (OTH) AF: 0.181 AC: 381 AN: 2106

Alfa AF: 0.211 Hom.: 506

Bravo AF: 0.180

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.60
PhyloP100		-1.0
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: rs13146124; hg19: chr4-185391408;