rs3733475

Variant names:

• chr4-184473956-G-T
• rs3733475
• NM_002199.4:c.-7+423C>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+423C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,112 control chromosomes in the GnomAD database, including 9,563 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 0.33 (9540 hom., cov: 30)
  • Exomes 𝑓: 0.36 (23 hom.)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• Publications: 3 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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	NM_002199.4	MANE Select	c.-7+423C>A		intron	N/A	NP_002190.2	P14316-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF2	ENST00000393593.8	TSL:1 MANE Select	c.-7+423C>A		intron	N/A	ENSP00000377218.3	P14316-1
	IRF2	ENST00000505067.6	TSL:3	c.-7+13C>A		intron	N/A	ENSP00000421927.2	K4DIA4
	IRF2	ENST00000883917.1		c.-7+423C>A		intron	N/A	ENSP00000553976.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49513 AN: 151662 Hom.: 9532 Cov.: 30

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.358 AC: 119 AN: 332 Hom.: 23 Cov.: 0 AF XY: 0.359 AC XY: 84 AN XY: 234

African (AFR) AF: 0.0833 AC: 1 AN: 12

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 0.300 AC: 3 AN: 10

South Asian (SAS) AF: 0.367 AC: 11 AN: 30

European-Finnish (FIN) AF: 0.417 AC: 5 AN: 12

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.387 AC: 92 AN: 238

Other (OTH) AF: 0.167 AC: 3 AN: 18

GnomAD4 genome AF: 0.326 AC: 49533 AN: 151780 Hom.: 9540 Cov.: 30 AF XY: 0.329 AC XY: 24416 AN XY: 74160

African (AFR) AF: 0.115 AC: 4743 AN: 41398

American (AMR) AF: 0.449 AC: 6850 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1326 AN: 3466

East Asian (EAS) AF: 0.483 AC: 2485 AN: 5150

South Asian (SAS) AF: 0.353 AC: 1694 AN: 4804

European-Finnish (FIN) AF: 0.402 AC: 4226 AN: 10516

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27055 AN: 67880

Other (OTH) AF: 0.361 AC: 759 AN: 2104

Alfa AF: 0.348 Hom.: 1334

Bravo AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		0.17
PromoterAI		-0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3733475; hg19: chr4-185395110;