Variant rs79518579 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 NM_000404.4(GLB1):c.792+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 1,614,012 control chromosomes in the GnomAD database, including 1,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 353 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1229 hom. )

Consequence

GLB1
NM_000404.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.818

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=-0.82).

BP6

Variant 3-33053481-C-A is Benign according to our data. Variant chr3-33053481-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 92914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 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.792+10G>T		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.792+10G>T		intron_variant		1	NM_000404.4	ENSP00000306920.4		P16278

Frequencies

GnomAD3 genomes

AF:

0.0548

AC:

8341

AN:

152084

Hom.:

347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0360

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.0717

Gnomad SAS

AF:

0.0476

Gnomad FIN

AF:

0.0196

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0308

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0398

AC:

9930

AN:

249468

Hom.:

289

AF XY:

0.0394

AC XY:

5331

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.0361

Gnomad ASJ exome

AF:

0.0235

Gnomad EAS exome

AF:

0.0761

Gnomad SAS exome

AF:

0.0511

Gnomad FIN exome

AF:

0.0211

Gnomad NFE exome

AF:

0.0272

Gnomad OTH exome

AF:

0.0345

GnomAD4 exome

AF:

0.0353

AC:

51543

AN:

1461810

Hom.:

1229

Cov.:

AF XY:

0.0353

AC XY:

25699

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.0370

Gnomad4 ASJ exome

AF:

0.0222

Gnomad4 EAS exome

AF:

0.0719

Gnomad4 SAS exome

AF:

0.0513

Gnomad4 FIN exome

AF:

0.0212

Gnomad4 NFE exome

AF:

0.0306

Gnomad4 OTH exome

AF:

0.0425

GnomAD4 genome

AF:

0.0551

AC:

8379

AN:

152202

Hom.:

353

Cov.:

AF XY:

0.0541

AC XY:

4029

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.0359

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.0717

Gnomad4 SAS

AF:

0.0474

Gnomad4 FIN

AF:

0.0196

Gnomad4 NFE

AF:

0.0308

Gnomad4 OTH

AF:

0.0487

Alfa

AF:

0.0184

Hom.:

Bravo

AF:

0.0593

Asia WGS

AF:

0.0740

AC:

258

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 27, 2015	- -

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 03, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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;C0086652:Mucopolysaccharidosis, MPS-IV-B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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. -

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

-0.82

CADD

Benign

3.1

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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