rs3830444

Variant names:

• chr7-65979372-T-TGA
• rs3830444
• NM_000181.4:c.724+25_724+26dupTC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0400
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000181.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUSB	NM_000181.4	MANE Select	c.724+25_724+26dupTC		intron	N/A	NP_000172.2
	GUSB	NM_001284290.2		c.474+460_474+461dupTC		intron	N/A	NP_001271219.1
	GUSB	NM_001293104.2		c.154+25_154+26dupTC		intron	N/A	NP_001280033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUSB	ENST00000304895.9	TSL:1 MANE Select	c.724+26_724+27insTC		intron	N/A	ENSP00000302728.4
	GUSB	ENST00000446111.1	TSL:1	n.*117+13_*117+14insTC		intron	N/A	ENSP00000416793.1
	GUSB	ENST00000421103.5	TSL:2	c.474+461_474+462insTC		intron	N/A	ENSP00000391390.1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74866 AN: 151732 Hom.: 19508 Cov.: 0

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

GnomAD2 exomes AF: 0.562 AC: 140822 AN: 250538 AF XY: 0.567

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 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.: 34 AF XY: 0.547 AC XY: 396225 AN XY: 724786

African (AFR) AF: 0.324 AC: 10821 AN: 33382

American (AMR) AF: 0.536 AC: 23951 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 16169 AN: 26104

East Asian (EAS) AF: 0.864 AC: 34276 AN: 39674

South Asian (SAS) AF: 0.619 AC: 53261 AN: 86104

European-Finnish (FIN) AF: 0.607 AC: 32359 AN: 53318

Middle Eastern (MID) AF: 0.590 AC: 2813 AN: 4770

European-Non Finnish (NFE) AF: 0.527 AC: 584342 AN: 1108394

Other (OTH) AF: 0.546 AC: 32789 AN: 60082

GnomAD4 genome AF: 0.493 AC: 74912 AN: 151852 Hom.: 19520 Cov.: 0 AF XY: 0.499 AC XY: 37044 AN XY: 74206

African (AFR) AF: 0.337 AC: 13958 AN: 41428

American (AMR) AF: 0.509 AC: 7750 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2107 AN: 3464

East Asian (EAS) AF: 0.810 AC: 4173 AN: 5152

South Asian (SAS) AF: 0.643 AC: 3097 AN: 4816

European-Finnish (FIN) AF: 0.595 AC: 6269 AN: 10532

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35743 AN: 67922

Other (OTH) AF: 0.509 AC: 1070 AN: 2104

Alfa AF: 0.539 Hom.: 3733

Bravo AF: 0.485

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 14, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: no assertion criteria provided

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.040
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3830444; hg19: chr7-65444359;