rs3775574

Variant names:

• chr4-184448912-G-A
• rs3775574
• NM_002199.4:c.-6-19842C>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.-6-19842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,014 control chromosomes in the GnomAD database, including 20,061 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 0.47 (20053 hom., cov: 32)
  • Exomes 𝑓: 0.60 (8 hom.)
• Consequence: IRF2 NM_002199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2	NM_002199.4	c.-6-19842C>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.-6-19842C>T		intron_variant	Intron 1 of 8	1	NM_002199.4	ENSP00000377218.3

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71620 AN: 151866 Hom.: 20044 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.550

GnomAD4 exome AF: 0.600 AC: 18 AN: 30 Hom.: 8 Cov.: 0 AF XY: 0.636 AC XY: 14 AN XY: 22

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 4 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.714 AC: 10 AN: 14

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.471 AC: 71636 AN: 151984 Hom.: 20053 Cov.: 32 AF XY: 0.473 AC XY: 35156 AN XY: 74292

African (AFR) AF: 0.156 AC: 6471 AN: 41466

American (AMR) AF: 0.597 AC: 9115 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2223 AN: 3472

East Asian (EAS) AF: 0.382 AC: 1973 AN: 5170

South Asian (SAS) AF: 0.517 AC: 2490 AN: 4812

European-Finnish (FIN) AF: 0.580 AC: 6104 AN: 10532

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41373 AN: 67964

Other (OTH) AF: 0.545 AC: 1145 AN: 2102

Alfa AF: 0.571 Hom.: 110063

Bravo AF: 0.462

Asia WGS AF: 0.432 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.71
PhyloP100		-0.13
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: rs3775574; hg19: chr4-185370066;