19-18178088-T-G

Variant names:

• chr19-18178088-T-G
• rs1045747
• ENST00000593731.1:n.*2366T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000593731.1(ENSG00000268173):​n.*2366T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000203 in 493,484 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: ENSG00000268173 ENST00000593731.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988
• Publications: 0 publications found

Genes affected

ENSG00000268173 (HGNC:):

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI30	NM_006332.5	c.*177T>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000407280.4	NP_006323.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000268173	ENST00000593731.1	n.*2366T>G		non_coding_transcript_exon_variant	Exon 25 of 25	2		ENSP00000471914.1
IFI30	ENST00000407280.4	c.*177T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_006332.5	ENSP00000384886.1
ENSG00000268173	ENST00000593731.1	n.*2366T>G		3_prime_UTR_variant	Exon 25 of 25	2		ENSP00000471914.1
IFI30	ENST00000600463.1	n.2087T>G		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000203 AC: 1 AN: 493484 Hom.: 0 Cov.: 5 AF XY: 0.00000382 AC XY: 1 AN XY: 261894

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 13514

American (AMR) AF: 0.00 AC: 0 AN: 23942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15100

East Asian (EAS) AF: 0.00 AC: 0 AN: 31394

South Asian (SAS) AF: 0.00 AC: 0 AN: 49300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2102

European-Non Finnish (NFE) AF: 0.00000337 AC: 1 AN: 296640

Other (OTH) AF: 0.00 AC: 0 AN: 27594

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.61
DANN	Benign	0.24
PhyloP100		-0.99

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: rs1045747; hg19: chr19-18288898;