Genetic Variant NM_000181.4:c.724+25_724+26dupTC (chr7-65979372-T-TGA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000181.4(GUSB):c.724+25_724+26dupTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,608,378 control chromosomes in the GnomAD database, including 238,717 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19520 hom., cov: 0)

Exomes 𝑓: 0.54 ( 219197 hom. )

Consequence

GUSB
NM_000181.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0400

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 -16 ACMG points.

BP6

Variant 7-65979372-T-TGA is Benign according to our data. Variant chr7-65979372-T-TGA is described in ClinVar as [Benign]. Clinvar id is 92591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUSB	NM_000181.4 link	c.724+25_724+26dupTC		intron_variant	Intron 4 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.724+26_724+27insTC		intron_variant	Intron 4 of 11	1	NM_000181.4	ENSP00000302728.4		P08236-1

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74866

AN:

151732

Hom.:

19508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.614

Gnomad AMR

AF:

0.509

Gnomad ASJ

AF:

0.608

Gnomad EAS

AF:

0.809

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.595

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.505

GnomAD3 exomes

AF:

0.562

AC:

140822

AN:

250538

Hom.:

40908

AF XY:

0.567

AC XY:

76824

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.330

Gnomad AMR exome

AF:

0.542

Gnomad ASJ exome

AF:

0.626

Gnomad EAS exome

AF:

0.808

Gnomad SAS exome

AF:

0.626

Gnomad FIN exome

AF:

0.612

Gnomad NFE exome

AF:

0.529

Gnomad OTH exome

AF:

0.561

GnomAD4 exome

AF:

0.543

AC:

790781

AN:

1456526

Hom.:

219197

Cov.:

AF XY:

0.547

AC XY:

396225

AN XY:

724786

show subpopulations

Gnomad4 AFR exome

AF:

0.324

Gnomad4 AMR exome

AF:

0.536

Gnomad4 ASJ exome

AF:

0.619

Gnomad4 EAS exome

AF:

0.864

Gnomad4 SAS exome

AF:

0.619

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.527

Gnomad4 OTH exome

AF:

0.546

GnomAD4 genome

AF:

0.493

AC:

74912

AN:

151852

Hom.:

19520

Cov.:

AF XY:

0.499

AC XY:

37044

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.337

Gnomad4 AMR

AF:

0.509

Gnomad4 ASJ

AF:

0.608

Gnomad4 EAS

AF:

0.810

Gnomad4 SAS

AF:

0.643

Gnomad4 FIN

AF:

0.595

Gnomad4 NFE

AF:

0.526

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.539

Hom.:

3733

Bravo

AF:

0.485

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Oct 14, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mucopolysaccharidosis type 7

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Oct 23, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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