chr3-32973977-G-T

Position:

• chr3-32973977-G-T

Variant summary

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

The NM_001393580.1(GLB1):​c.1735-12356C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,788 control chromosomes in the GnomAD database, including 16,194 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 0.43 (16194 hom., cov: 30)
• Consequence: GLB1 NM_001393580.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLB1	NM_001393580.1	c.1735-12356C>A		intron_variant			NP_001380509.1
		n.32973977G>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64997 AN: 151672 Hom.: 16194 Cov.: 30

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.403

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.428 AC: 65019 AN: 151788 Hom.: 16194 Cov.: 30 AF XY: 0.433 AC XY: 32137 AN XY: 74158

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.408

Alfa AF: 0.503 Hom.: 33784

Bravo AF: 0.401

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13314993; hg19: chr3-33015469;