rs6780220

Positions:

• chr3-33045708-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000404.4(GLB1):​c.1068+412T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,075,154 control chromosomes in the GnomAD database, including 17,601 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3295 hom., cov: 31)
  • Exomes 𝑓: 0.17 (14306 hom.)
• Consequence: GLB1 NM_000404.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLB1	NM_000404.4	c.1068+412T>G		intron_variant		ENST00000307363.10	NP_000395.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLB1	ENST00000307363.10	c.1068+412T>G		intron_variant		1	NM_000404.4	ENSP00000306920	P2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28840 AN: 151888 Hom.: 3281 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.169 AC: 156050 AN: 923148 Hom.: 14306 Cov.: 32 AF XY: 0.170 AC XY: 73334 AN XY: 431498

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.557

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.190 AC: 28890 AN: 152006 Hom.: 3295 Cov.: 31 AF XY: 0.195 AC XY: 14485 AN XY: 74286

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.172

Alfa AF: 0.167 Hom.: 3940

Bravo AF: 0.186

Asia WGS AF: 0.380 AC: 1322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.21

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

Other links and lift over

dbSNP: rs6780220; hg19: chr3-33087200;