ENST00000508166.5:c.59-15634A>G

Variant names:

• chr4-22720347-A-G
• rs10030690
• ENST00000508166.5:c.59-15634A>G

Variant summary

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

The ENST00000508166.5(GBA3):​c.59-15634A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,020 control chromosomes in the GnomAD database, including 15,653 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 0.44 (15653 hom., cov: 32)
• Consequence: GBA3 ENST00000508166.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 1 publications found

Genes affected

GBA3 (HGNC:19069): (glucosylceramidase beta 3 (gene/pseudogene)) The protein encoded by this gene is a cytosolic enzyme that can hydrolyze several types of glycosides. The enzyme has its highest activity at neutral pH and is predominantly expressed in human liver, kidney, intestine, and spleen. This gene is a polymorphic pseudogene, with the most common allele being the functional allele that encodes the full-length protein. Some individuals contain a single nucleotide polymorphism that results in a premature stop codon in the coding region, and therefore this allele is pseudogenic due to the failure to produce a functional full-length protein. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2022]

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 (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000508166.5. 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
	GBA3	NR_102355.2		n.138-15634A>G		intron	N/A
	GBA3	NR_102356.2		n.138-15634A>G		intron	N/A
	GBA3	NR_102357.2		n.59+6197A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBA3	ENST00000508166.5	TSL:1	c.59-15634A>G		intron	N/A	ENSP00000427458.1
	GBA3	ENST00000503442.1	TSL:1	c.59-15634A>G		intron	N/A	ENSP00000422220.1
	GBA3	ENST00000511446.2	TSL:2	c.-456+6197A>G		intron	N/A	ENSP00000423754.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67457 AN: 151900 Hom.: 15615 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.444 AC: 67545 AN: 152020 Hom.: 15653 Cov.: 32 AF XY: 0.443 AC XY: 32899 AN XY: 74308

African (AFR) AF: 0.588 AC: 24368 AN: 41452

American (AMR) AF: 0.432 AC: 6606 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1474 AN: 5170

South Asian (SAS) AF: 0.239 AC: 1150 AN: 4818

European-Finnish (FIN) AF: 0.417 AC: 4397 AN: 10542

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26762 AN: 67974

Other (OTH) AF: 0.434 AC: 914 AN: 2106

Alfa AF: 0.393 Hom.: 6342

Bravo AF: 0.454

Asia WGS AF: 0.300 AC: 1040 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.68
DANN	Benign	0.50
PhyloP100		-0.38

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: rs10030690; hg19: chr4-22721970;