rs6856910

Variant names:

• chr4-184391201-C-T
• rs6856910
• NM_002199.4:c.695-452G>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.695-452G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,104 control chromosomes in the GnomAD database, including 29,413 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 0.61 (29413 hom., cov: 33)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.695-452G>A		intron_variant	Intron 7 of 8	ENST00000393593.8	NP_002190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2	ENST00000393593.8	c.695-452G>A		intron_variant	Intron 7 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93412 AN: 151986 Hom.: 29402 Cov.: 33

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.614 AC: 93463 AN: 152104 Hom.: 29413 Cov.: 33 AF XY: 0.617 AC XY: 45875 AN XY: 74340

African (AFR) AF: 0.469 AC: 19459 AN: 41496

American (AMR) AF: 0.670 AC: 10246 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2264 AN: 3468

East Asian (EAS) AF: 0.618 AC: 3187 AN: 5158

South Asian (SAS) AF: 0.662 AC: 3190 AN: 4822

European-Finnish (FIN) AF: 0.668 AC: 7067 AN: 10572

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45967 AN: 67980

Other (OTH) AF: 0.595 AC: 1253 AN: 2106

Alfa AF: 0.649 Hom.: 63832

Bravo AF: 0.609

Asia WGS AF: 0.597 AC: 2078 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	5.1
DANN	Benign	0.19
PhyloP100		-0.31
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: rs6856910; hg19: chr4-185312355;