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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • 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_000527.5(LDLR):c.148G>A (p.Ala50Thr)

CA041995

251037 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: bda5bdbf-7033-4175-9630-76a62e1686bc
Approved on: 2024-10-28
Published on: 2025-01-20

HGVS expressions

NM_000527.5:c.148G>A
NM_000527.5(LDLR):c.148G>A (p.Ala50Thr)
NC_000019.10:g.11100303G>A
CM000681.2:g.11100303G>A
NC_000019.9:g.11210979G>A
CM000681.1:g.11210979G>A
NC_000019.8:g.11071979G>A
NG_009060.1:g.15923G>A
ENST00000252444.10:c.406G>A
ENST00000559340.2:c.148G>A
ENST00000560467.2:c.148G>A
ENST00000558518.6:c.148G>A
ENST00000252444.9:c.402G>A
ENST00000455727.6:c.148G>A
ENST00000535915.5:c.148G>A
ENST00000545707.5:c.148G>A
ENST00000557933.5:c.148G>A
ENST00000557958.1:n.234G>A
ENST00000558013.5:c.148G>A
ENST00000558518.5:c.148G>A
ENST00000560502.5:n.234G>A
NM_000527.4:c.148G>A
NM_001195798.1:c.148G>A
NM_001195799.1:c.148G>A
NM_001195800.1:c.148G>A
NM_001195803.1:c.148G>A
NM_001195798.2:c.148G>A
NM_001195799.2:c.148G>A
NM_001195800.2:c.148G>A
NM_001195803.2:c.148G>A
More

Uncertain Significance

Not Met criteria codes 23
BS2 BS4 BS3 BS1 PS2 PS4 PS3 PS1 PVS1 BP2 BP3 BP4 BP7 BA1 PP4 PP1 PP3 PM3 PM1 PM4 PM5 PM6 PM2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.148G>A (p.Ala50Thr) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying no ACMG/AMP evidence codes as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on October 28th, 2024.
Not Met criteria codes
BS2
No data available.
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No data available.
BS1
FAF = 0.00003900 (0.003900%) in African/African American exomes+genomes (gnomAD v4.1.0).
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Variant doesn't meet PM2.
PS3
No data available.
PS1
No other missense variant with the same amino acid change.
PVS1
Not a null variant
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No in-frame deletions/insertions
BP4
REVEL= 0.599. It is not below 0.5.
BP7
Not a synonymous (silent) variant
BA1
FAF = 0.00003900 (0.003900%) in African/African American exomes+genomes (gnomAD v4.1.0).
PP4
Variant doesn't meet PM2.
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
REVEL= 0.599. It is not above 0.75. Splicing evaluation required. A) variant not on limits. B) variant is exonic and at least 50bp downstream from the canonical acceptor site, but it does not create GT. C) No GT nearby. Variant is not predicted to alter splicing.
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not on exon 4. Not a cysteine residue.
PM4
No in-frame deletions/insertions
PM5
1 other missense variants in the same codon: - NM_000527.5(LDLR):c.148G>T (p.Ala50Ser) (ClinVar ID 68099) - Unknown significance by these guidelines There is no variant in the same codon classified as Pathogenic by these guidelines
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
PopMax MAF = 0.0008396 (0.083%) in African/African American exomes+genomes (gnomAD v4.1.0).
Curation History
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