Variant chr1-155234903-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000157.4(GBA1):c.*92G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 1 hom., cov: 4)

Exomes 𝑓: 0.012 ( 39 hom. )

Failed GnomAD Quality Control

Consequence

GBA1
NM_000157.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.523

Variant links:

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]

GBA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-155234903-C-T is Benign according to our data. Variant chr1-155234903-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1809693.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0121 (5040/416414) while in subpopulation NFE AF= 0.014 (3437/245778). AF 95% confidence interval is 0.0136. There are 39 homozygotes in gnomad4_exome. There are 2569 alleles in male gnomad4_exome subpopulation. Median coverage is 3. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GBA1	NM_000157.4 linkuse as main transcript	c.*92G>A		3_prime_UTR_variant	11/11	ENST00000368373.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GBA1	ENST00000368373.8 linkuse as main transcript	c.*92G>A		3_prime_UTR_variant	11/11	1	NM_000157.4	P1	P04062-1

Frequencies

GnomAD3 genomes

AF:

0.00705

AC:

129

AN:

18300

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00468

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00970

Gnomad ASJ

AF:

0.00830

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.0146

Gnomad FIN

AF:

0.00319

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00822

Gnomad OTH

AF:

0.00313

GnomAD4 exome

AF:

0.0121

AC:

5040

AN:

416414

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

2569

AN XY:

219344

show subpopulations

Gnomad4 AFR exome

AF:

0.00451

Gnomad4 AMR exome

AF:

0.0121

Gnomad4 ASJ exome

AF:

0.00812

Gnomad4 EAS exome

AF:

0.00971

Gnomad4 SAS exome

AF:

0.00902

Gnomad4 FIN exome

AF:

0.00714

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.0132

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00711

AC:

130

AN:

18284

Hom.:

Cov.:

AF XY:

0.00719

AC XY:

AN XY:

8344

show subpopulations

Gnomad4 AFR

AF:

0.00511

Gnomad4 AMR

AF:

0.00970

Gnomad4 ASJ

AF:

0.00830

Gnomad4 EAS

AF:

0.00350

Gnomad4 SAS

AF:

0.0136

Gnomad4 FIN

AF:

0.00319

Gnomad4 NFE

AF:

0.00824

Gnomad4 OTH

AF:

0.00311

Alfa

AF:

0.0432

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Gaucher disease type II;C0268251:Gaucher disease type III;C0752347:Lewy body dementia;C1842704:Gaucher disease perinatal lethal;C1856476:Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome;C1961835:Gaucher disease type I;C3160718:Parkinson disease, late-onset

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.2

DANN

Benign

0.61

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