rs11554159

Variant names:

• chr19-18175134-G-A
• rs11554159
• NM_006332.5:c.227G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-18175134-G-A
• chr19-18175134-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 73 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI30	NM_006332.5	MANE Select	c.227G>A	p.Arg76Gln	missense	Exon 2 of 7	NP_006323.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI30	ENST00000407280.4	TSL:1 MANE Select	c.227G>A	p.Arg76Gln	missense	Exon 2 of 7	ENSP00000384886.1
	ENSG00000268173	ENST00000593731.1	TSL:2	n.*1663G>A		non_coding_transcript_exon	Exon 20 of 25	ENSP00000471914.1
	ENSG00000268173	ENST00000593731.1	TSL:2	n.*1663G>A		3_prime_UTR	Exon 20 of 25	ENSP00000471914.1

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

GnomAD2 exomes AF: 0.228 AC: 55720 AN: 244546 AF XY: 0.232

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 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

African (AFR) AF: 0.237 AC: 7923 AN: 33446

American (AMR) AF: 0.173 AC: 7649 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 8545 AN: 26044

East Asian (EAS) AF: 0.0798 AC: 3162 AN: 39648

South Asian (SAS) AF: 0.191 AC: 16441 AN: 85920

European-Finnish (FIN) AF: 0.253 AC: 13452 AN: 53236

Middle Eastern (MID) AF: 0.319 AC: 1838 AN: 5762

European-Non Finnish (NFE) AF: 0.270 AC: 299600 AN: 1110736

Other (OTH) AF: 0.255 AC: 15387 AN: 60298

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

African (AFR) AF: 0.236 AC: 9778 AN: 41486

American (AMR) AF: 0.201 AC: 3075 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3468

East Asian (EAS) AF: 0.0701 AC: 362 AN: 5162

South Asian (SAS) AF: 0.171 AC: 825 AN: 4816

European-Finnish (FIN) AF: 0.256 AC: 2710 AN: 10576

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18176 AN: 67966

Other (OTH) AF: 0.261 AC: 551 AN: 2110

Alfa AF: 0.253 Hom.: 16252

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 v4.9

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
Eigen	Benign	0.053
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.8
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.36
Sift	Benign	0.083	T
Sift4G	Uncertain	0.028	D
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
Mutation Taster		=94/6	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: rs11554159; hg19: chr19-18285944; COSMIC: COSV55847770; COSMIC: COSV55847770;