Variant 7-65960934-G-GCTA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PM4_SupportingBP6_Very_StrongBS1

The NM_000181.4(GUSB):c.1918_1919insTAG(p.Val639dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,613,954 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000082 ( 2 hom. )

Consequence

GUSB
NM_000181.4 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: -0.340

Variant links:

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]

GUSB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000181.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 7-65960934-G-GCTA is Benign according to our data. Variant chr7-65960934-G-GCTA is described in ClinVar as [Likely_benign]. Clinvar id is 590834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000105 (16/152164) while in subpopulation EAS AF= 0.0031 (16/5166). AF 95% confidence interval is 0.00194. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUSB	NM_000181.4 linkuse as main transcript	c.1918_1919insTAG	p.Val639dup	inframe_insertion	12/12	ENST00000304895.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUSB	ENST00000304895.9 linkuse as main transcript	c.1918_1919insTAG	p.Val639dup	inframe_insertion	12/12	1	NM_000181.4	P1	P08236-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000231

AC:

AN:

251470

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00315

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000821

AC:

120

AN:

1461790

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00290

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000105

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00310

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000170

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mucopolysaccharidosis type 7

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 16, 2024	- -
Uncertain significance, no assertion criteria provided	curation	SingHealth Duke-NUS Institute of Precision Medicine	Jun 07, 2017	- -

GUSB-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 12, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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