dbSNP rs34204221: GLB1:c.458-11T>C (chr3-33065568-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000404.4(GLB1):c.458-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,562,346 control chromosomes in the GnomAD database, including 10,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 906 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9112 hom. )

Consequence

GLB1
NM_000404.4 intron

Scores

Splicing: ADA: 0.0001366

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.00600

Variant links:

Genes affected

GLB1 (HGNC:4298): (galactosidase beta 1) This gene encodes a member of the glycosyl hydrolase 35 family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature lysosomal enzyme. This enzyme catalyzes the hydrolysis of a terminal beta-linked galactose residue from ganglioside substrates and other glycoconjugates. Mutations in this gene may result in GM1-gangliosidosis and Morquio B syndrome. [provided by RefSeq, Nov 2015]

GLB1 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=-0.81).

BP6

Variant 3-33065568-A-G is Benign according to our data. Variant chr3-33065568-A-G is described in ClinVar as [Benign]. Clinvar id is 92909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-33065568-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLB1	NM_000404.4 link	c.458-11T>C		intron_variant	Intron 4 of 15	ENST00000307363.10	NP_000395.3	P16278

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLB1	ENST00000307363.10 link	c.458-11T>C		intron_variant	Intron 4 of 15	1	NM_000404.4	ENSP00000306920.4		P16278

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15585

AN:

152144

Hom.:

906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0568

Gnomad ASJ

AF:

0.0954

Gnomad EAS

AF:

0.0169

Gnomad SAS

AF:

0.0528

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.0860

GnomAD3 exomes

AF:

0.0872

AC:

14889

AN:

170666

Hom.:

777

AF XY:

0.0858

AC XY:

7796

AN XY:

90870

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.0392

Gnomad ASJ exome

AF:

0.0896

Gnomad EAS exome

AF:

0.0168

Gnomad SAS exome

AF:

0.0469

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.0844

GnomAD4 exome

AF:

0.110

AC:

155760

AN:

1410084

Hom.:

9112

Cov.:

AF XY:

0.109

AC XY:

75945

AN XY:

696458

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.0418

Gnomad4 ASJ exome

AF:

0.0927

Gnomad4 EAS exome

AF:

0.0166

Gnomad4 SAS exome

AF:

0.0485

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.103

AC:

15611

AN:

152262

Hom.:

906

Cov.:

AF XY:

0.0997

AC XY:

7420

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0568

Gnomad4 ASJ

AF:

0.0954

Gnomad4 EAS

AF:

0.0170

Gnomad4 SAS

AF:

0.0528

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.0851

Alfa

AF:

0.114

Hom.:

327

Bravo

AF:

0.0968

Asia WGS

AF:

0.0370

AC:

127

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 20, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 18, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Dec 16, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mucopolysaccharidosis, MPS-IV-B

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GM1 gangliosidosis

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GM1 gangliosidosis;C0086652:Mucopolysaccharidosis, MPS-IV-B

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Infantile GM1 gangliosidosis

Benign:1

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.9

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.060

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