rs273265

Positions:

• chr19-18173526-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000597802.2(IFI30):​c.-38-278A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 299,368 control chromosomes in the GnomAD database, including 8,826 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 0.26 (5243 hom., cov: 31)
  • Exomes 𝑓: 0.21 (3583 hom.)
• Consequence: IFI30 ENST00000597802.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997

Genes affected

IFI30 (HGNC:5398): (IFI30 lysosomal thiol reductase) The protein encoded by this gene is a lysosomal thiol reductase that at low pH can reduce protein disulfide bonds. The enzyme is expressed constitutively in antigen-presenting cells and induced by gamma-interferon in other cell types. This enzyme has an important role in MHC class II-restricted antigen processing. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFI30	ENST00000597802.2	c.-38-278A>G		intron_variant		3		ENSP00000470527

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38957 AN: 151752 Hom.: 5212 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.209 AC: 30835 AN: 147498 Hom.: 3583 AF XY: 0.203 AC XY: 15788 AN XY: 77790

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.257 AC: 39051 AN: 151870 Hom.: 5243 Cov.: 31 AF XY: 0.257 AC XY: 19056 AN XY: 74258

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.260

Alfa AF: 0.250 Hom.: 614

Bravo AF: 0.263

Asia WGS AF: 0.173 AC: 599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.032
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs273265; hg19: chr19-18284336;