rs17057419

Variant names:

• chr8-27579871-A-G
• rs17057419

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.222 in 152,060 control chromosomes in the GnomAD database, including 4,527 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 0.22 (4527 hom., cov: 32)
• Consequence: GULOP intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 5 publications found

Genes affected

GULOP (HGNC:4695): (gulonolactone (L-) oxidase, pseudogene) This gene is nonfunctional in humans and other primates. In most mammalian species the corresponding gene encodes L-gulono-gamma-lactone oxidase which catalyzes the last step of ascorbic acid biosynthesis. The human gene is a remnant that lacks five of twelve exons found in functional rodent genes. The loss of enzyme activity results in hypoascorbemia or the inability to synthesize vitamin C. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GULOP		n.27579871A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GULOP	ENST00000454030.1	n.304+2154A>G		intron_variant	Intron 3 of 5	6

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33703 AN: 151940 Hom.: 4529 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.211

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33735 AN: 152060 Hom.: 4527 Cov.: 32 AF XY: 0.221 AC XY: 16448 AN XY: 74306

African (AFR) AF: 0.344 AC: 14265 AN: 41468

American (AMR) AF: 0.214 AC: 3272 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 821 AN: 3472

East Asian (EAS) AF: 0.430 AC: 2216 AN: 5158

South Asian (SAS) AF: 0.344 AC: 1651 AN: 4800

European-Finnish (FIN) AF: 0.0670 AC: 710 AN: 10604

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10122 AN: 67962

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.173 Hom.: 5046

Bravo AF: 0.238

Asia WGS AF: 0.374 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.30
PhyloP100		-1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17057419; hg19: chr8-27437388;