7-65982195-C-T

Position:

• chr7-65982195-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000181.4(GUSB):​c.-12G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,499,816 control chromosomes in the GnomAD database, including 409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (62 hom., cov: 31)
  • Exomes 𝑓: 0.0092 (347 hom.)
• Consequence: GUSB NM_000181.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.73

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-65982195-C-T is Benign according to our data. Variant chr7-65982195-C-T is described in ClinVar as [Benign]. Clinvar id is 360558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUSB	NM_000181.4	c.-12G>A		5_prime_UTR_variant	1/12	ENST00000304895.9	NP_000172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUSB	ENST00000304895.9	c.-12G>A		5_prime_UTR_variant	1/12	1	NM_000181.4	ENSP00000302728	P1

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2835 AN: 152248 Hom.: 59 Cov.: 31

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.00889

Gnomad FIN AF: 0.0622

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00522

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.0213 AC: 2371 AN: 111254 Hom.: 71 AF XY: 0.0182 AC XY: 1127 AN XY: 61888

Gnomad AFR exome AF: 0.0255

Gnomad AMR exome AF: 0.0404

Gnomad ASJ exome AF: 0.00557

Gnomad EAS exome AF: 0.0876

Gnomad SAS exome AF: 0.00515

Gnomad FIN exome AF: 0.0558

Gnomad NFE exome AF: 0.00391

Gnomad OTH exome AF: 0.0197

GnomAD4 exome AF: 0.00922 AC: 12420 AN: 1347450 Hom.: 347 Cov.: 30 AF XY: 0.00903 AC XY: 5969 AN XY: 661160

Gnomad4 AFR exome AF: 0.0212

Gnomad4 AMR exome AF: 0.0366

Gnomad4 ASJ exome AF: 0.00617

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.00605

Gnomad4 FIN exome AF: 0.0542

Gnomad4 NFE exome AF: 0.00326

Gnomad4 OTH exome AF: 0.0157

GnomAD4 genome AF: 0.0187 AC: 2855 AN: 152366 Hom.: 62 Cov.: 31 AF XY: 0.0213 AC XY: 1587 AN XY: 74510

Gnomad4 AFR AF: 0.0206

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.0897

Gnomad4 SAS AF: 0.00869

Gnomad4 FIN AF: 0.0622

Gnomad4 NFE AF: 0.00522

Gnomad4 OTH AF: 0.0250

Alfa AF: 0.0110 Hom.: 4

Bravo AF: 0.0166

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mucopolysaccharidosis type 7 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 19, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 16, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.96
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs2279903; hg19: chr7-65447182;