rs10216623

Variant names:

• chr8-27583362-G-A
• rs10216623

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 0.106 in 152,238 control chromosomes in the GnomAD database, including 921 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 0.11 (921 hom., cov: 33)
• Consequence: GULOP intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GULOP		n.27583362G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GULOP	ENST00000454030.1	n.305-2598G>A		intron_variant	Intron 3 of 5	6

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16172 AN: 152120 Hom.: 926 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.106 AC: 16192 AN: 152238 Hom.: 921 Cov.: 33 AF XY: 0.106 AC XY: 7925 AN XY: 74442

African (AFR) AF: 0.102 AC: 4235 AN: 41542

American (AMR) AF: 0.125 AC: 1910 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1094 AN: 5172

South Asian (SAS) AF: 0.149 AC: 719 AN: 4816

European-Finnish (FIN) AF: 0.0480 AC: 509 AN: 10612

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6921 AN: 68010

Other (OTH) AF: 0.113 AC: 240 AN: 2116

Alfa AF: 0.115 Hom.: 2900

Bravo AF: 0.114

Asia WGS AF: 0.196 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.91
DANN	Benign	0.47
PhyloP100		-0.92

Splicing

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

Other links and lift over

dbSNP: rs10216623; hg19: chr8-27440879;