19-18173891-TG-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_006332.5(IFI30):c.52del(p.Asp18ThrfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000552 in 1,551,202 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (5 hom.)
• Consequence: IFI30 NM_006332.5 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.11

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 19-18173891-TG-T is Benign according to our data. Variant chr19-18173891-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI30	NM_006332.5	c.52del	p.Asp18ThrfsTer15	frameshift_variant	1/7	ENST00000407280.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFI30	ENST00000407280.4	c.52del	p.Asp18ThrfsTer15	frameshift_variant	1/7	1	NM_006332.5	P1
IFI30	ENST00000597802.2	c.52del	p.Asp18ThrfsTer15	frameshift_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.000585 AC: 89 AN: 152264 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000866 AC: 133 AN: 153628 Hom.: 2 AF XY: 0.000835 AC XY: 68 AN XY: 81456

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00187

Gnomad ASJ exome AF: 0.000942

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00136

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000665

Gnomad OTH exome AF: 0.00206

GnomAD4 exome AF: 0.000548 AC: 767 AN: 1398820 Hom.: 5 Cov.: 32 AF XY: 0.000555 AC XY: 383 AN XY: 689950

Gnomad4 AFR exome AF: 0.0000633

Gnomad4 AMR exome AF: 0.00207

Gnomad4 ASJ exome AF: 0.000517

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00148

Gnomad4 FIN exome AF: 0.0000620

Gnomad4 NFE exome AF: 0.000371

Gnomad4 OTH exome AF: 0.00112

GnomAD4 genome AF: 0.000584 AC: 89 AN: 152382 Hom.: 1 Cov.: 32 AF XY: 0.000644 AC XY: 48 AN XY: 74522

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.000714

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

IFI30: BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs764788458; hg19: chr19-18284701;