chr19-18175086-C-T

Variant names:

• chr19-18175086-C-T
• rs140704918
• NM_006332.5:c.179C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006332.5(IFI30):​c.179C>T​(p.Pro60Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,613,836 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (8 hom.)
• Consequence: IFI30 NM_006332.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.286
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00481534).
• BP6: Variant 19-18175086-C-T is Benign according to our data. Variant chr19-18175086-C-T is described in ClinVar as Benign. ClinVar VariationId is 2649574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006332.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI30	NM_006332.5	MANE Select	c.179C>T	p.Pro60Leu	missense	Exon 2 of 7	NP_006323.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI30	ENST00000407280.4	TSL:1 MANE Select	c.179C>T	p.Pro60Leu	missense	Exon 2 of 7	ENSP00000384886.1	P13284
	ENSG00000268173	ENST00000593731.1	TSL:2	n.*1615C>T		non_coding_transcript_exon	Exon 20 of 25	ENSP00000471914.1
	ENSG00000268173	ENST00000593731.1	TSL:2	n.*1615C>T		3_prime_UTR	Exon 20 of 25	ENSP00000471914.1

Frequencies

GnomAD3 genomes AF: 0.00244 AC: 372 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00852

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00229

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00235 AC: 585 AN: 248576 AF XY: 0.00231

Gnomad AFR exome AF: 0.000912

Gnomad AMR exome AF: 0.00525

Gnomad ASJ exome AF: 0.0109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00225

Gnomad OTH exome AF: 0.00414

GnomAD4 exome AF: 0.00293 AC: 4288 AN: 1461556 Hom.: 8 Cov.: 31 AF XY: 0.00279 AC XY: 2027 AN XY: 727046

African (AFR) AF: 0.000687 AC: 23 AN: 33474

American (AMR) AF: 0.00532 AC: 238 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 289 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86228

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00320 AC: 3553 AN: 1111802

Other (OTH) AF: 0.00288 AC: 174 AN: 60366

GnomAD4 genome AF: 0.00244 AC: 372 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.00259 AC XY: 193 AN XY: 74470

African (AFR) AF: 0.000698 AC: 29 AN: 41554

American (AMR) AF: 0.00851 AC: 130 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00229 AC: 156 AN: 68024

Other (OTH) AF: 0.00569 AC: 12 AN: 2108

Alfa AF: 0.00280 Hom.: 1

Bravo AF: 0.00305

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000754 AC: 3

ESP6500EA AF: 0.00265 AC: 22

ExAC AF: 0.00197 AC: 238

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00320

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.085	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.29
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.053
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.010	B
Vest4		0.14
MVP		0.12
MPC		0.019
ClinPred		0.025	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.089
gMVP		0.61
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs140704918; hg19: chr19-18285896;