Variant rs73438754 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000378103.7(GBA2):c.1795+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00793 in 1,610,666 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 214 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 217 hom. )

Consequence

GBA2
ENST00000378103.7 splice_region, intron

Scores

Splicing: ADA: 0.0001650

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.00100

Variant links:

Genes affected

GBA2 (HGNC:18986): (glucosylceramidase beta 2) This gene encodes a microsomal beta-glucosidase that catalyzes the hydrolysis of bile acid 3-O-glucosides as endogenous compounds. Studies to determine subcellular localization of this protein in the liver indicated that the enzyme was mainly enriched in the microsomal fraction where it appeared to be confined to the endoplasmic reticulum. This putative transmembrane protein is thought to play a role in carbohydrate transport and metabolism. [provided by RefSeq, Jul 2008]

GBA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 9-35738995-C-T is Benign according to our data. Variant chr9-35738995-C-T is described in ClinVar as [Benign]. Clinvar id is 416641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBA2	NM_020944.3 linkuse as main transcript	c.1795+7G>A		splice_region_variant, intron_variant		ENST00000378103.7	NP_065995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBA2	ENST00000378103.7 linkuse as main transcript	c.1795+7G>A		splice_region_variant, intron_variant		1	NM_020944.3	ENSP00000367343	P1	Q9HCG7-1

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

4737

AN:

152062

Hom.:

214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00232

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.00940

AC:

2347

AN:

249766

Hom.:

AF XY:

0.00705

AC XY:

952

AN XY:

135002

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.00564

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00358

Gnomad NFE exome

AF:

0.00225

Gnomad OTH exome

AF:

0.00608

GnomAD4 exome

AF:

0.00550

AC:

8020

AN:

1458486

Hom.:

217

Cov.:

AF XY:

0.00487

AC XY:

3534

AN XY:

725554

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.00598

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000314

Gnomad4 FIN exome

AF:

0.00435

Gnomad4 NFE exome

AF:

0.00306

Gnomad4 OTH exome

AF:

0.00835

GnomAD4 genome

AF:

0.0312

AC:

4754

AN:

152180

Hom.:

214

Cov.:

AF XY:

0.0300

AC XY:

2231

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00232

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0155

Hom.:

Bravo

AF:

0.0354

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00202

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 27, 2024

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 14, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Oct 29, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.4

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over