ClinVar Genomic variation as it relates to human health
NM_000181.4(GUSB):c.1946T>C (p.Leu649Pro)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000181.4(GUSB):c.1946T>C (p.Leu649Pro)
Variation ID: 92588 Accession: VCV000092588.58
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q11.21 7: 65960907 (GRCh38) [ NCBI UCSC ] 7: 65425894 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 2, 2016 Feb 20, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000181.4:c.1946T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000172.2:p.Leu649Pro missense NM_001284290.2:c.1508T>C NP_001271219.1:p.Leu503Pro missense NM_001293104.2:c.1376T>C NP_001280033.1:p.Leu459Pro missense NM_001293105.2:c.1289T>C NP_001280034.1:p.Leu430Pro missense NR_120531.2:n.1891T>C non-coding transcript variant NC_000007.14:g.65960907A>G NC_000007.13:g.65425894A>G NG_016197.1:g.26408T>C NG_051954.1:g.92809A>G P08236:p.Leu649Pro - Protein change
- L649P, L430P, L503P, L459P
- Other names
- -
- Canonical SPDI
- NC_000007.14:65960906:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.41933 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.49085
The Genome Aggregation Database (gnomAD) 0.50676
Trans-Omics for Precision Medicine (TOPMed) 0.50747
1000 Genomes Project 30x 0.57121
Exome Aggregation Consortium (ExAC) 0.57963
1000 Genomes Project 0.58067
The Genome Aggregation Database (gnomAD), exomes 0.58528
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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GUSB | - | - |
GRCh38 GRCh37 |
592 | 651 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign (4) |
criteria provided, multiple submitters, no conflicts
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Apr 16, 2018 | RCV000078327.24 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000394365.23 | |
Benign (2) |
criteria provided, single submitter
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Jul 31, 2018 | RCV000675829.15 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000302896.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Mar 28, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000539264.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 58% of total chromosomes in ExAC (less)
Method: Genome/Exome Filtration
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Benign
(Oct 14, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000110173.8
First in ClinVar: Jan 17, 2014 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 20
Sex: mixed
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Benign
(Apr 16, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000919480.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: GUSB c.1946T>C (p.Leu649Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign … (more)
Variant summary: GUSB c.1946T>C (p.Leu649Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.58 in 276996 control chromosomes, suggesting that it is the major allele and therefore benign. To our knowledge, no occurrence of c.1946T>C in individuals affected with Mucopolysaccharidosis Type VI (Sly Syndrome) and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. (less)
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Benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis type 7
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000469755.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
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 … (more)
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. (less)
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Benign
(Jul 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001891996.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
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Benign
(Aug 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis type 7
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001934060.1
First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis type 7
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001732007.5
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
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Benign
(Oct 20, 2015)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000801552.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GUSB | - | - | - | - |
Text-mined citations for rs9530 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.