rs879010457

Positions:

• chr7-65961067-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000181.4(GUSB):​c.1790-4G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0075 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GUSB NM_000181.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002440
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.296

Genes affected

GUSB (HGNC:4696): (glucuronidase beta) This gene encodes a hydrolase that degrades glycosaminoglycans, including heparan sulfate, dermatan sulfate, and chondroitin-4,6-sulfate. The enzyme forms a homotetramer that is localized to the lysosome. Mutations in this gene result in mucopolysaccharidosis type VII. Alternative splicing results in multiple transcript variants. There are many pseudogenes of this locus in the human genome.[provided by RefSeq, May 2014]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-65961067-C-A is Benign according to our data. Variant chr7-65961067-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 458509.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUSB	NM_000181.4	c.1790-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000304895.9	NP_000172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUSB	ENST00000304895.9	c.1790-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000181.4	ENSP00000302728	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 217 AN: 106558 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.00117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000592

Gnomad ASJ AF: 0.000377

Gnomad EAS AF: 0.000263

Gnomad SAS AF: 0.00171

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00192

Gnomad OTH AF: 0.00205

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00748 AC: 10087 AN: 1348104 Hom.: 0 Cov.: 35 AF XY: 0.00794 AC XY: 5355 AN XY: 674436

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.0451

Gnomad4 ASJ exome AF: 0.0128

Gnomad4 EAS exome AF: 0.00615

Gnomad4 SAS exome AF: 0.0195

Gnomad4 FIN exome AF: 0.0401

Gnomad4 NFE exome AF: 0.00300

Gnomad4 OTH exome AF: 0.00654

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00205 AC: 218 AN: 106592 Hom.: 0 Cov.: 29 AF XY: 0.00222 AC XY: 113 AN XY: 50814

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.000591

Gnomad4 ASJ AF: 0.000377

Gnomad4 EAS AF: 0.000264

Gnomad4 SAS AF: 0.00172

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.00192

Gnomad4 OTH AF: 0.00204

Alfa AF: 0.00451 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mucopolysaccharidosis type 7 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.17
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.016
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: rs879010457; hg19: chr7-65426054;