rs708606

Variant names:

• chr1-155234903-C-T
• rs708606
• NM_000157.4:c.*92G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.523

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=-0.9).
• 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 rank	MANE	Protein	UniProt
GBA1	NM_000157.4	c.*92G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000368373.8	NP_000148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBA1	ENST00000368373	c.*92G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_000157.4	ENSP00000357357.3

Frequencies

GnomAD3 genomes AF: 0.00705 AC: 129 AN: 18300 Hom.: 1 Cov.: 4

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.: 39 Cov.: 3 AF XY: 0.0117 AC XY: 2569 AN XY: 219344

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.: 1 Cov.: 4 AF XY: 0.00719 AC XY: 60 AN XY: 8344

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.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Oct 04, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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

Other links and lift over

dbSNP: rs708606; hg19: chr1-155204694; COSMIC: COSV59168994; COSMIC: COSV59168994;