Variant 7-65974892-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000181.4(GUSB):c.1065+27C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,609,890 control chromosomes in the GnomAD database, including 255,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21189 hom., cov: 31)

Exomes 𝑓: 0.56 ( 234316 hom. )

Consequence

GUSB
NM_000181.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.831

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-65974892-G-C is Benign according to our data. Variant chr7-65974892-G-C is described in ClinVar as [Benign]. Clinvar id is 92583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUSB	NM_000181.4 linkuse as main transcript	c.1065+27C>G		intron_variant		ENST00000304895.9	NP_000172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUSB	ENST00000304895.9 linkuse as main transcript	c.1065+27C>G		intron_variant		1	NM_000181.4	ENSP00000302728	P1	P08236-1

Frequencies

GnomAD3 genomes

AF:

0.516

AC:

78409

AN:

151862

Hom.:

21178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.628

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.621

Gnomad EAS

AF:

0.807

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.656

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.530

GnomAD3 exomes

AF:

0.578

AC:

144984

AN:

250980

Hom.:

42913

AF XY:

0.582

AC XY:

78951

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.361

Gnomad AMR exome

AF:

0.552

Gnomad ASJ exome

AF:

0.635

Gnomad EAS exome

AF:

0.806

Gnomad SAS exome

AF:

0.621

Gnomad FIN exome

AF:

0.624

Gnomad NFE exome

AF:

0.554

Gnomad OTH exome

AF:

0.577

GnomAD4 exome

AF:

0.562

AC:

819768

AN:

1457910

Hom.:

234316

Cov.:

AF XY:

0.565

AC XY:

410106

AN XY:

725412

show subpopulations

Gnomad4 AFR exome

AF:

0.359

Gnomad4 AMR exome

AF:

0.546

Gnomad4 ASJ exome

AF:

0.631

Gnomad4 EAS exome

AF:

0.862

Gnomad4 SAS exome

AF:

0.614

Gnomad4 FIN exome

AF:

0.622

Gnomad4 NFE exome

AF:

0.550

Gnomad4 OTH exome

AF:

0.564

GnomAD4 genome

AF:

0.516

AC:

78456

AN:

151980

Hom.:

21189

Cov.:

AF XY:

0.522

AC XY:

38767

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.371

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.621

Gnomad4 EAS

AF:

0.807

Gnomad4 SAS

AF:

0.637

Gnomad4 FIN

AF:

0.612

Gnomad4 NFE

AF:

0.549

Gnomad4 OTH

AF:

0.534

Alfa

AF:

0.486

Hom.:

2691

Bravo

AF:

0.506

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 14, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 20, 2015	- -

Mucopolysaccharidosis type 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.9

DANN

Benign

0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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