rs77226678

Positions:

chr3-32997255-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000307363.10(GLB1):c.1824G>C(p.Leu608=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,614,126 control chromosomes in the GnomAD database, including 4,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 508 hom., cov: 32)

Exomes 𝑓: 0.020 ( 3860 hom. )

Consequence

GLB1
ENST00000307363.10 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.172

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 -21 ACMG points.

BP4

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

BP6

Variant 3-32997255-C-G is Benign according to our data. Variant chr3-32997255-C-G is described in ClinVar as [Benign]. Clinvar id is 92902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.172 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 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.1824G>C	p.Leu608=	synonymous_variant	16/16	ENST00000307363.10	NP_000395.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GLB1	ENST00000307363.10 linkuse as main transcript	c.1824G>C	p.Leu608=	synonymous_variant	16/16	1	NM_000404.4	ENSP00000306920	P2
GLB1	ENST00000307377.12 linkuse as main transcript	c.1431G>C	p.Leu477=	synonymous_variant	13/13	1		ENSP00000305920
GLB1	ENST00000399402.7 linkuse as main transcript	c.1734G>C	p.Leu578=	synonymous_variant	16/16	2		ENSP00000382333	A2

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3333

AN:

152118

Hom.:

514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.0976

Gnomad FIN

AF:

0.0235

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00279

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0458

AC:

11430

AN:

249464

Hom.:

1786

AF XY:

0.0466

AC XY:

6305

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.00303

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.423

Gnomad SAS exome

AF:

0.0873

Gnomad FIN exome

AF:

0.0246

Gnomad NFE exome

AF:

0.00279

Gnomad OTH exome

AF:

0.0248

GnomAD4 exome

AF:

0.0200

AC:

29207

AN:

1461890

Hom.:

3860

Cov.:

AF XY:

0.0221

AC XY:

16038

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.405

Gnomad4 SAS exome

AF:

0.0864

Gnomad4 FIN exome

AF:

0.0250

Gnomad4 NFE exome

AF:

0.00208

Gnomad4 OTH exome

AF:

0.0292

GnomAD4 genome

AF:

0.0218

AC:

3326

AN:

152236

Hom.:

508

Cov.:

AF XY:

0.0263

AC XY:

1955

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00344

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.418

Gnomad4 SAS

AF:

0.0974

Gnomad4 FIN

AF:

0.0235

Gnomad4 NFE

AF:

0.00279

Gnomad4 OTH

AF:

0.0228

Alfa

AF:

0.00624

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.192

AC:

664

AN:

3478

EpiCase

AF:

0.00251

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 16, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 04, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Mucopolysaccharidosis, MPS-IV-B

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

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

-0.75

CADD

Benign

7.2

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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