8-27586760-A-G

Position:

• chr8-27586760-A-G

Variant summary

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

The ENST00000454030.1(GULOP):​n.456-185A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. 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 ENST00000454030.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GULOP	ENST00000454030.1	n.456-185A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0446

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.000777

Gnomad4 SAS AF: 0.0466

Gnomad4 FIN AF: 0.0349

Gnomad4 NFE AF: 0.0725

Gnomad4 OTH AF: 0.0574

Alfa AF: 0.0716 Hom.: 472

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs881146; hg19: chr8-27444277;