rs7125

Variant names:

• chr19-18177259-A-G
• rs7125
• NM_006332.5:c.603A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-18177259-A-G
• chr19-18177259-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006332.5(IFI30):​c.603A>G​(p.Pro201Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,584,048 control chromosomes in the GnomAD database, including 206,270 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 0.52 (20841 hom., cov: 32)
  • Exomes 𝑓: 0.50 (185429 hom.)
• Consequence: IFI30 NM_006332.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.19
• Publications: 38 publications found

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]

ENSG00000268173 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP7: Synonymous conserved (PhyloP=-5.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI30	NM_006332.5	c.603A>G	p.Pro201Pro	synonymous_variant	Exon 5 of 7	ENST00000407280.4	NP_006323.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFI30	ENST00000407280.4	c.603A>G	p.Pro201Pro	synonymous_variant	Exon 5 of 7	1	NM_006332.5	ENSP00000384886.1
ENSG00000268173	ENST00000593731.1	n.*2039A>G		non_coding_transcript_exon_variant	Exon 23 of 25	2		ENSP00000471914.1
ENSG00000268173	ENST00000593731.1	n.*2039A>G		3_prime_UTR_variant	Exon 23 of 25	2		ENSP00000471914.1
IFI30	ENST00000600463.1	n.1342A>G		non_coding_transcript_exon_variant	Exon 4 of 5	2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78665 AN: 151960 Hom.: 20799 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.547

GnomAD2 exomes AF: 0.472 AC: 96762 AN: 205208 AF XY: 0.467

Gnomad AFR exome AF: 0.562

Gnomad AMR exome AF: 0.476

Gnomad ASJ exome AF: 0.618

Gnomad EAS exome AF: 0.210

Gnomad FIN exome AF: 0.508

Gnomad NFE exome AF: 0.517

Gnomad OTH exome AF: 0.510

GnomAD4 exome AF: 0.504 AC: 721123 AN: 1431970 Hom.: 185429 Cov.: 50 AF XY: 0.500 AC XY: 354530 AN XY: 709368

African (AFR) AF: 0.575 AC: 18848 AN: 32804

American (AMR) AF: 0.477 AC: 19009 AN: 39872

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 15631 AN: 25572

East Asian (EAS) AF: 0.197 AC: 7546 AN: 38400

South Asian (SAS) AF: 0.343 AC: 28157 AN: 81982

European-Finnish (FIN) AF: 0.511 AC: 26187 AN: 51254

Middle Eastern (MID) AF: 0.600 AC: 3439 AN: 5728

European-Non Finnish (NFE) AF: 0.522 AC: 572110 AN: 1097010

Other (OTH) AF: 0.509 AC: 30196 AN: 59348

GnomAD4 genome AF: 0.518 AC: 78778 AN: 152078 Hom.: 20841 Cov.: 32 AF XY: 0.515 AC XY: 38278 AN XY: 74360

African (AFR) AF: 0.567 AC: 23510 AN: 41478

American (AMR) AF: 0.511 AC: 7806 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2048 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1078 AN: 5170

South Asian (SAS) AF: 0.332 AC: 1600 AN: 4826

European-Finnish (FIN) AF: 0.513 AC: 5423 AN: 10580

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35680 AN: 67960

Other (OTH) AF: 0.546 AC: 1152 AN: 2110

Alfa AF: 0.525 Hom.: 65394

Bravo AF: 0.523

Asia WGS AF: 0.294 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.20
DANN	Benign	0.24
PhyloP100		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs7125; hg19: chr19-18288069; COSMIC: COSV69576413; COSMIC: COSV69576413;