rs13093698

Positions:

chr3-33021558-A-G

Variant summary

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

The NM_000404.4(GLB1):c.1233+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,612,234 control chromosomes in the GnomAD database, including 37,411 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3418 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33993 hom. )

Consequence

GLB1
NM_000404.4 splice_region, intron

Scores

Splicing: ADA: 0.00002256

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12O:1

Conservation

PhyloP100: 2.80

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:

GLB1 (HGNC:):

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=-0.67).

BP6

Variant 3-33021558-A-G is Benign according to our data. Variant chr3-33021558-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 92894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-33021558-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLB1	NM_000404.4 linkuse as main transcript	c.1233+8T>C		splice_region_variant, intron_variant		ENST00000307363.10	NP_000395.3	P16278

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLB1	ENST00000307363.10 linkuse as main transcript	c.1233+8T>C		splice_region_variant, intron_variant		1	NM_000404.4	ENSP00000306920.4		P16278

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31572

AN:

152040

Hom.:

3417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.0516

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.197

GnomAD3 exomes

AF:

0.194

AC:

48010

AN:

246848

Hom.:

4885

AF XY:

0.193

AC XY:

25822

AN XY:

133826

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.224

Gnomad EAS exome

AF:

0.0569

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.213

AC:

310751

AN:

1460076

Hom.:

33993

Cov.:

AF XY:

0.211

AC XY:

153326

AN XY:

726178

show subpopulations

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.229

Gnomad4 EAS exome

AF:

0.0598

Gnomad4 SAS exome

AF:

0.157

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.224

Gnomad4 OTH exome

AF:

0.209

GnomAD4 genome

AF:

0.208

AC:

31608

AN:

152158

Hom.:

3418

Cov.:

AF XY:

0.204

AC XY:

15167

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.222

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.0518

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.197

Gnomad4 NFE

AF:

0.223

Gnomad4 OTH

AF:

0.199

Alfa

AF:

0.218

Hom.:

2181

Bravo

AF:

0.207

Asia WGS

AF:

0.139

AC:

482

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 27, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3Other:1

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	phenotyping only	GenomeConnect - GM1	-	Variant interpreted as Benign and reported on 09-25-2014 by Lab or GTR ID 239772. GenomeConnect-GM1 assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 15, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Mucopolysaccharidosis, MPS-IV-B

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -

GM1 gangliosidosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Infantile GM1 gangliosidosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000023

dbscSNV1_RF

Benign

0.030

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