1-155236550-T-G

Variant names:

• chr1-155236550-T-G
• rs9628662
• NM_000157.4:c.1000-81A>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000157.4(GBA1):​c.1000-81A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,142,664 control chromosomes in the GnomAD database, including 69,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12483 hom., cov: 31)
  • Exomes 𝑓: 0.32 (57135 hom.)
• Consequence: GBA1 NM_000157.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.292

Genes affected

GBA1 (HGNC:4177): (glucosylceramidase beta 1) This gene encodes a lysosomal membrane protein that cleaves the beta-glucosidic linkage of glycosylceramide, an intermediate in glycolipid metabolism. Mutations in this gene cause Gaucher disease, a lysosomal storage disease characterized by an accumulation of glucocerebrosides. A related pseudogene is approximately 12 kb downstream of this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-155236550-T-G is Benign according to our data. Variant chr1-155236550-T-G is described in ClinVar as [Benign]. Clinvar id is 828082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBA1	NM_000157.4	c.1000-81A>C		intron_variant	Intron 7 of 10	ENST00000368373.8	NP_000148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBA1	ENST00000368373.8	c.1000-81A>C		intron_variant	Intron 7 of 10	1	NM_000157.4	ENSP00000357357.3

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58841 AN: 151774 Hom.: 12448 Cov.: 31

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.322 AC: 319472 AN: 990772 Hom.: 57135 AF XY: 0.321 AC XY: 163314 AN XY: 508656

Gnomad4 AFR exome AF: 0.543

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.730

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.314

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.388 AC: 58918 AN: 151892 Hom.: 12483 Cov.: 31 AF XY: 0.388 AC XY: 28776 AN XY: 74252

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.363

Alfa AF: 0.310 Hom.: 8685

Bravo AF: 0.401

Asia WGS AF: 0.555 AC: 1930 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 37% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 34. Only high quality variants are reported. -

Gaucher disease Benign:1

May 20, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.81
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs9628662; hg19: chr1-155206341;