rs11554159

chr19-18175134-G-Achr19-18175134-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006332.5(IFI30):c.227G>A(p.Arg76Gln) variant causes a missense change. The variant allele was found at a frequency of 0.255 in 1,611,462 control chromosomes in the GnomAD database, including 53,986 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 0.24 (4531 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49455 hom.)
• Consequence: IFI30 NM_006332.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017537773).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI30	NM_006332.5	c.227G>A	p.Arg76Gln	missense_variant	2/7	ENST00000407280.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFI30	ENST00000407280.4	c.227G>A	p.Arg76Gln	missense_variant	2/7	1	NM_006332.5	P1
IFI30	ENST00000597802.2	c.227G>A	p.Arg76Gln	missense_variant	3/3	3
IFI30	ENST00000600463.1	n.966G>A		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36820 AN: 151942 Hom.: 4528 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.265

GnomAD3 exomes AF: 0.228 AC: 55720 AN: 244546 Hom.: 6860 AF XY: 0.232 AC XY: 30885 AN XY: 132846

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.0773

Gnomad SAS exome AF: 0.190

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.256 AC: 373997 AN: 1459402 Hom.: 49455 Cov.: 36 AF XY: 0.256 AC XY: 185515 AN XY: 725784

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.0798

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.242 AC: 36837 AN: 152060 Hom.: 4531 Cov.: 32 AF XY: 0.240 AC XY: 17823 AN XY: 74334

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.0701

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.261

Alfa AF: 0.254 Hom.: 6629

Bravo AF: 0.243

TwinsUK AF: 0.267 AC: 990

ALSPAC AF: 0.279 AC: 1076

ESP6500AA AF: 0.219 AC: 905

ESP6500EA AF: 0.256 AC: 2157

ExAC AF: 0.224 AC: 27090

Asia WGS AF: 0.117 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.27
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.095	T;T
Eigen	Benign	0.053
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T;D
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.000095	P
PrimateAI	Uncertain	0.52	T
Sift4G	Uncertain	0.028	D;T
Polyphen		1.0	.;D
Vest4		0.14
MPC		0.087
ClinPred		0.032	T
GERP RS		4.2
Varity_R		0.28
gMVP		0.65

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: rs11554159; hg19: chr19-18285944; COSMIC: COSV55847770; COSMIC: COSV55847770;