Variant 19-18175086-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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. 13/19 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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.286

Variant links:

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]

IFI30 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 2649574.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-18175086-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI30	NM_006332.5 linkuse as main transcript	c.179C>T	p.Pro60Leu	missense_variant	2/7	ENST00000407280.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IFI30	ENST00000407280.4 linkuse as main transcript	c.179C>T	p.Pro60Leu	missense_variant	2/7	1	NM_006332.5	P1
IFI30	ENST00000597802.2 linkuse as main transcript	c.179C>T	p.Pro60Leu	missense_variant	3/3	3
IFI30	ENST00000600463.1 linkuse as main transcript	n.918C>T		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.00244

AC:

372

AN:

152162

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00235

AC:

585

AN:

248576

Hom.:

AF XY:

0.00231

AC XY:

312

AN XY:

134930

show subpopulations

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 SAS exome

AF:

0.0000654

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.:

Cov.:

AF XY:

0.00279

AC XY:

2027

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00532

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00320

Gnomad4 OTH exome

AF:

0.00288

GnomAD4 genome

AF:

0.00244

AC:

372

AN:

152280

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00851

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00281

Hom.:

Bravo

AF:

0.00305

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000754

AC:

ESP6500EA

AF:

0.00265

AC:

ExAC

AF:

0.00197

AC:

238

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00320

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

PIK3R2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.085

T;D

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.48

T;T

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.010

.;B

Vest4

0.14

MVP

0.12

MPC

0.019

ClinPred

0.025

GERP RS

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.089

gMVP

0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over