Genetic Variant GUSB:c.1653+151A>G (chr7-65967580-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000181.4(GUSB):c.1653+151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 718,606 control chromosomes in the GnomAD database, including 118,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20730 hom., cov: 32)

Exomes 𝑓: 0.58 ( 97915 hom. )

Consequence

GUSB
NM_000181.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.05

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-65967580-T-C is Benign according to our data. Variant chr7-65967580-T-C is described in ClinVar as [Benign]. Clinvar id is 528232.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 rank	MANE	Protein	UniProt
GUSB	NM_000181.4 link	c.1653+151A>G		intron_variant	Intron 10 of 11	ENST00000304895.9	NP_000172.2	P08236-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUSB	ENST00000304895.9 link	c.1653+151A>G		intron_variant	Intron 10 of 11	1	NM_000181.4	ENSP00000302728.4		P08236-1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77219

AN:

151906

Hom.:

20718

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.626

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.807

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.550

Gnomad OTH

AF:

0.521

GnomAD4 exome

AF:

0.580

AC:

328406

AN:

566582

Hom.:

97915

AF XY:

0.582

AC XY:

178612

AN XY:

306878

show subpopulations

African (AFR)

AF:

0.337

AC:

5511

AN:

16336

American (AMR)

AF:

0.543

AC:

19152

AN:

35264

Ashkenazi Jewish (ASJ)

AF:

0.632

AC:

12294

AN:

19460

East Asian (EAS)

AF:

0.872

AC:

27935

AN:

32024

South Asian (SAS)

AF:

0.618

AC:

39748

AN:

64322

European-Finnish (FIN)

AF:

0.619

AC:

21201

AN:

34238

Middle Eastern (MID)

AF:

0.606

AC:

1538

AN:

2538

European-Non Finnish (NFE)

AF:

0.554

AC:

183782

AN:

331836

Other (OTH)

AF:

0.564

AC:

17245

AN:

30564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

7372

14743

22115

29486

36858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.508

AC:

77265

AN:

152024

Hom.:

20730

Cov.:

AF XY:

0.514

AC XY:

38173

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.343

AC:

14206

AN:

41464

American (AMR)

AF:

0.523

AC:

7988

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2144

AN:

3470

East Asian (EAS)

AF:

0.808

AC:

4161

AN:

5152

South Asian (SAS)

AF:

0.638

AC:

3073

AN:

4814

European-Finnish (FIN)

AF:

0.612

AC:

6458

AN:

10560

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.550

AC:

37364

AN:

67988

Other (OTH)

AF:

0.525

AC:

1107

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1910

3820

5731

7641

9551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.516

Hom.:

2713

Bravo

AF:

0.497

Asia WGS

AF:

0.702

AC:

2442

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 24, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mucopolysaccharidosis type 7

Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.74

(source)

DANN

Benign

0.59

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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7-65967580-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over