rs79518579

Variant names:

• chr3-33053481-C-A
• rs79518579
• NM_000404.4:c.792+10G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-33053481-C-A
• chr3-33053481-C-G
• chr3-33053481-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.818
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• GM1 gangliosidosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women’s Health
• GM1 gangliosidosis type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
• mucopolysaccharidosis type 4B

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• GM1 gangliosidosis type 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
• GM1 gangliosidosis type 2

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000404.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLB1	NM_000404.4	MANE Select	c.792+10G>T		intron	N/A	NP_000395.3
	GLB1	NM_001317040.2		c.936+10G>T		intron	N/A	NP_001303969.2
	GLB1	NM_001079811.3		c.702+10G>T		intron	N/A	NP_001073279.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLB1	ENST00000307363.10	TSL:1 MANE Select	c.792+10G>T		intron	N/A	ENSP00000306920.4	P16278
	GLB1	ENST00000307377.12	TSL:1	c.399+10G>T		intron	N/A	ENSP00000305920.8	E7EQ29
	GLB1	ENST00000399402.7	TSL:2	c.702+10G>T		intron	N/A	ENSP00000382333.2	P16278

Frequencies

GnomAD3 genomes AF: 0.0548 AC: 8341 AN: 152084 Hom.: 347 Cov.: 32

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

GnomAD2 exomes AF: 0.0398 AC: 9930 AN: 249468 AF XY: 0.0394

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 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.: 32 AF XY: 0.0353 AC XY: 25699 AN XY: 727188

African (AFR) AF: 0.120 AC: 4010 AN: 33472

American (AMR) AF: 0.0370 AC: 1656 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 580 AN: 26132

East Asian (EAS) AF: 0.0719 AC: 2855 AN: 39698

South Asian (SAS) AF: 0.0513 AC: 4424 AN: 86252

European-Finnish (FIN) AF: 0.0212 AC: 1134 AN: 53414

Middle Eastern (MID) AF: 0.0420 AC: 242 AN: 5768

European-Non Finnish (NFE) AF: 0.0306 AC: 34078 AN: 1111954

Other (OTH) AF: 0.0425 AC: 2564 AN: 60396

GnomAD4 genome AF: 0.0551 AC: 8379 AN: 152202 Hom.: 353 Cov.: 32 AF XY: 0.0541 AC XY: 4029 AN XY: 74428

African (AFR) AF: 0.114 AC: 4714 AN: 41516

American (AMR) AF: 0.0359 AC: 549 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3470

East Asian (EAS) AF: 0.0717 AC: 371 AN: 5176

South Asian (SAS) AF: 0.0474 AC: 229 AN: 4828

European-Finnish (FIN) AF: 0.0196 AC: 208 AN: 10602

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0308 AC: 2092 AN: 68000

Other (OTH) AF: 0.0487 AC: 103 AN: 2114

Alfa AF: 0.0210 Hom.: 11

Bravo AF: 0.0593

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Mucopolysaccharidosis, MPS-IV-B (2)
-	-	1	GM1 gangliosidosis (1)
-	-	1	GM1 gangliosidosis;C0086652:Mucopolysaccharidosis, MPS-IV-B (1)
-	-	1	Infantile GM1 gangliosidosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.57
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79518579; hg19: chr3-33094973; COSMIC: COSV56565706; COSMIC: COSV56565706;