Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Link to SEPIO compliant JSON-LD document
  • There was no gene found in the curated document received from the VCI/VCEP
  • No CSPEC related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000527.4(LDLR):c.-217C>T

CA10584691

250927 (ClinVar)

Gene: N/A
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 39f1f763-d020-4c98-b299-b417769cbe17
Approved on: 2023-11-07
Published on: 2024-09-25

HGVS expressions

NM_000527.4(LDLR):c.-217C>T
NC_000019.10:g.11089332C>T
CM000681.2:g.11089332C>T
NC_000019.9:g.11200008C>T
CM000681.1:g.11200008C>T
NC_000019.8:g.11061008C>T
NG_009060.1:g.4952C>T
NR_163945.1:n.328G>A

Benign

Met criteria codes 2
BA1 BS3_Supporting
Not Met criteria codes 20
PS2 PS4 PS3 PS1 PP1 PP4 PP3 PM3 PM1 PM4 PM5 PM6 PM2 BS2 BS4 BS1 BP2 BP3 BP4 PVS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.4(LDLR):c.-217C>T variant is classified as Benign for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes BA1 and BS3_Supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 7 November 2023. The supporting evidence is as follows: BA1: FAF=0.01016 (1.016%) in African/African American Genomes (gnomAD v4.0.0). BS3_Supporting: Level 3 assay: PMID 10484771 (Scholtz CL et al., 1999): Heterologous cells (HepG2). Luciferase assays demonstrated 160% gene expression ---- functional study is consistent with no damaging effect.
Met criteria codes
BA1
FAF=0.01016 (1.016%) in African/African American Genomes (gnomAD v4.0.0). So, BA1 is met.
BS3_Supporting
Level 3 assays - PMID 10484771: Heterologous cells (HepG2), luciferase assays - results - 160% gene expression. So, BS3_Supporting is met.
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Variant does not meet PM2. So, PS4 is not met.
PS3
Level 3 assays - PMID 10484771: Heterologous cells (HepG2), luciferase assays - results - 160% gene expression.
PS1
Variant is in the promoter region
PP1
No data available
PP4
Variant does not meet PM2. So, PP4 is not met.
PP3
Variant is in the promoter region
PM3
No data available
PM1
Not in exon 4. Not a cysteine residue
PM4
No in-frame deletions/insertions
PM5
Variant is in the promoter region
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
FAF=0.01016 (1.016%) in African/African American Genomes (gnomAD v4.0.0).
BS2
No data available
BS4
No data available
BS1
FAF=0.01016 (1.016%) in African/African American Genomes (gnomAD v4.0.0).
BP2
No data available
BP3
No in-frame deletions/insertions
BP4
Variant is in the promoter region
PVS1
Not a null variant
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