ClinVar Genomic variation as it relates to human health
NM_000057.4(BLM):c.1479_1480del (p.Thr494fs)
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_000057.4(BLM):c.1479_1480del (p.Thr494fs)
Variation ID: 371108 Accession: VCV000371108.18
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 15q26.1 15: 90760851-90760852 (GRCh38) [ NCBI UCSC ] 15: 91304081-91304082 (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 Jan 6, 2017 May 1, 2024 Jan 17, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000057.4:c.1479_1480del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000048.1:p.Thr494fs frameshift NM_000057.4:c.1479_1480delTA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000057.3:c.1479_1480del NM_001287246.2:c.1479_1480del NP_001274175.1:p.Thr494fs frameshift NM_001287247.2:c.1479_1480del NP_001274176.1:p.Thr494fs frameshift NM_001287248.2:c.354_355del NP_001274177.1:p.Thr119fs frameshift NC_000015.10:g.90760852_90760853del NC_000015.9:g.91304082_91304083del NG_007272.1:g.48481_48482del LRG_20:g.48481_48482del LRG_20t1:c.1479_1480del - Protein change
- T119fs, T494fs
- Other names
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- Canonical SPDI
- NC_000015.10:90760850:ATA:A
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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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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BLM | - | - |
GRCh38 GRCh37 |
4372 | 4424 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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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Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 17, 2024 | RCV000409376.15 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 7, 2022 | RCV001011718.4 |
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
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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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Pathogenic
(Mar 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Bloom syndrome
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002107145.2
First in ClinVar: Mar 28, 2022 Last updated: Apr 02, 2022 |
Comment:
The c.1479_1480del;p.(Thr494Profs*9) is a null frameshift variant (NMD) in the BLM gene and predicts alteration of the nonsense-mediate decay - NMD is present in a … (more)
The c.1479_1480del;p.(Thr494Profs*9) is a null frameshift variant (NMD) in the BLM gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 371108). PS4_moderate. The variant is present at low allele frequencies population databases (rs746244182 – gnomAD 0.00007991%; ABraOM no frequency - http://abraom.ib.usp.br.) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Argentina
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Likely pathogenic
(Jun 28, 2016)
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criteria provided, single submitter
Method: clinical testing
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Bloom syndrome
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000486590.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
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Pathogenic
(Jan 17, 2024)
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criteria provided, single submitter
Method: clinical testing
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Bloom syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000749523.8
First in ClinVar: Jan 06, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Thr494Profs*9) in the BLM gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Thr494Profs*9) in the BLM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). This variant is present in population databases (rs746244182, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 371108). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Dec 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV001172073.5
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The c.1479_1480delTA pathogenic mutation, located in coding exon 6 of the BLM gene, results from a deletion of two nucleotides at nucleotide positions 1479 to … (more)
The c.1479_1480delTA pathogenic mutation, located in coding exon 6 of the BLM gene, results from a deletion of two nucleotides at nucleotide positions 1479 to 1480, causing a translational frameshift with a predicted alternate stop codon (p.T494Pfs*9). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Aug 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bloom syndrome
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004210871.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Bloom syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001460783.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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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Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry. | German J | Human mutation | 2007 | PMID: 17407155 |
Text-mined citations for rs746244182 ...
HelpRecord last updated Jun 23, 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.