8-27586760-A-G

Variant names:

• chr8-27586760-A-G
• rs881146

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 0.0492 in 151,984 control chromosomes in the GnomAD database, including 248 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 0.049 (248 hom., cov: 32)
• Consequence: GULOP intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GULOP		n.27586760A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GULOP	ENST00000454030.1	n.456-185A>G		intron_variant	Intron 4 of 5	6

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7481 AN: 151866 Hom.: 248 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.0470

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0725

Gnomad OTH AF: 0.0585

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

GnomAD4 genome AF: 0.0492 AC: 7476 AN: 151984 Hom.: 248 Cov.: 32 AF XY: 0.0467 AC XY: 3472 AN XY: 74290

African (AFR) AF: 0.0129 AC: 534 AN: 41482

American (AMR) AF: 0.0446 AC: 681 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3472

East Asian (EAS) AF: 0.000777 AC: 4 AN: 5148

South Asian (SAS) AF: 0.0466 AC: 223 AN: 4788

European-Finnish (FIN) AF: 0.0349 AC: 369 AN: 10582

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0725 AC: 4921 AN: 67914

Other (OTH) AF: 0.0574 AC: 121 AN: 2108

Alfa AF: 0.0694 Hom.: 608

Bravo AF: 0.0492

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.64
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs881146; hg19: chr8-27444277;