rs150466109

chr1-155240707-T-Cchr1-155240707-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000157.4(GBA1):c.38A>G(p.Lys13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 1,613,436 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (118 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (104 hom.)
• Consequence: GBA1 NM_000157.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.211

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018802583).
• BP6: Variant 1-155240707-T-C is Benign according to our data. Variant chr1-155240707-T-C is described in ClinVar as [Benign]. Clinvar id is 196296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-155240707-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GBA1	NM_000157.4	c.38A>G	p.Lys13Arg	missense_variant	2/11	ENST00000368373.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GBA1	ENST00000368373.8	c.38A>G	p.Lys13Arg	missense_variant	2/11	1	NM_000157.4	P1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3374 AN: 152110 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.0769

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00812

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.00565 AC: 1418 AN: 250914 Hom.: 36 AF XY: 0.00395 AC XY: 536 AN XY: 135608

Gnomad AFR exome AF: 0.0763

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00230 AC: 3354 AN: 1461208 Hom.: 104 Cov.: 31 AF XY: 0.00191 AC XY: 1385 AN XY: 726942

Gnomad4 AFR exome AF: 0.0784

Gnomad4 AMR exome AF: 0.00412

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000138

Gnomad4 OTH exome AF: 0.00545

GnomAD4 genome AF: 0.0222 AC: 3382 AN: 152228 Hom.: 118 Cov.: 32 AF XY: 0.0204 AC XY: 1517 AN XY: 74418

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.00811

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.00458 Hom.: 10

Bravo AF: 0.0253

ESP6500AA AF: 0.0708 AC: 312

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00705 AC: 856

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	May 16, 2017	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 12, 2021	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2018	This variant is associated with the following publications: (PMID: 32658388, 30302829, 26117366, 26296077, 28030538, 27884173, 17059888, 25525159, 22001711, 23588557) -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 15, 2016	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 04, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Gaucher disease Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Jun 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	4.8
Dann	Benign	0.66
DEOGEN2	Benign	0.34	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0080	N
MetaRNN	Benign	0.0019	T;T;T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	0.20	N;N;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.060	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.88	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.14
MVP		0.69
MPC		0.022
ClinPred		0.0030	T
GERP RS		-0.40
Varity_R		0.029
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs150466109; hg19: chr1-155210498;