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 computed assertion could be determined for this classification!

Variant: NM_000527.5(LDLR):c.940+9C>T

CA030486

328051 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 8c3b1786-8144-4427-b84f-02a77c574d68
Approved on: 2024-08-30
Published on: 2024-10-03

HGVS expressions

NM_000527.5:c.940+9C>T
NM_000527.5(LDLR):c.940+9C>T
NC_000019.10:g.11107523C>T
CM000681.2:g.11107523C>T
NC_000019.9:g.11218199C>T
CM000681.1:g.11218199C>T
NC_000019.8:g.11079199C>T
NG_009060.1:g.23143C>T
ENST00000252444.10:c.1198+9C>T
ENST00000559340.2:c.940+9C>T
ENST00000560467.2:c.940+9C>T
ENST00000558518.6:c.940+9C>T
ENST00000252444.9:c.1194+9C>T
ENST00000455727.6:c.436+9C>T
ENST00000535915.5:c.817+9C>T
ENST00000545707.5:c.559+9C>T
ENST00000557933.5:c.940+9C>T
ENST00000558013.5:c.940+9C>T
ENST00000558518.5:c.940+9C>T
ENST00000560467.1:c.540+9C>T
NM_000527.4:c.940+9C>T
NM_001195798.1:c.940+9C>T
NM_001195799.1:c.817+9C>T
NM_001195800.1:c.436+9C>T
NM_001195803.1:c.559+9C>T
NM_001195798.2:c.940+9C>T
NM_001195799.2:c.817+9C>T
NM_001195800.2:c.436+9C>T
NM_001195803.2:c.559+9C>T
More

Benign

Met criteria codes 2
BA1 BP4
Not Met criteria codes 24
PP1 PP4 PP3 PP2 PVS1 PM4 PM3 PM1 PM5 PM6 PM2 BS2 BS4 BS3 BS1 BP3 BP2 BP1 BP7 BP5 PS2 PS4 PS3 PS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Familial Hypercholesterolemia Expert Panel Specifications to the ACMG/AMP Variant Classification Guidelines Version 1.2

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR): c.940+9C>T variant is classified as Benign for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes BA1 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 30 August 2024. The supporting evidence is as follows: BA1: FAF = 0.02650 (2.650%) in African/African American exomes+genomes (gnomAD v4.1.0). BP4: No REVEL, splicing evaluation required. Functional data on splicing not available. A) variant not on limits. B) and C) variant is not exonic. Variant is not predicted to alter splicing.
Met criteria codes
BA1
FAF = 0.02650 (2.650%) in African/African American exomes+genomes (gnomAD v4.1.0), so BA1 is met.
BP4
No REVEL, splicing evaluation required. Functional data on splicing not available. A) variant not on limits B) and C) variant is not exonic. Variant is not predicted to alter splicing. --- BP4 is met.
Not Met criteria codes
PP1
No family members tested
PP4
Variant does not meet PM2 and is identified in 1 case with Simon-Broome criteria of possible FH from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière), France. Need at least 2 unrelated index cases, and also does not meet PM2, so PS4_Supporting is not met.
PP3
No REVEL, splicing evaluation required. Functional data on splicing not available. A) variant not on limits B) and C) variant is not exonic. Variant is not predicted to alter splicing. --- PP3 is not met.
PP2
not applicable
PVS1
variant is intronic and outside canonical splice sites, so not applicable
PM4
variant is intronic, so not applicable
PM3
not identified in index cases with more than 1 variant
PM1
variant is not missense, so not met
PM5
variant is not missense, so not applicable
PM6
no de novo occurrence
PM2
PopMax MAF = 0.02705 (2.705%) in African/African American (gnomAD v4.1.0). It is not below 0.02%, so not met
BS2
not identified in normolipidemic individuals
BS4
No family members tested
BS3
no published functional studies
BS1
FAF = 0.02650 (2.650%) in African/African American exomes+genomes (gnomAD v4.1.0), so BA1 is met.
BP3
not applicable
BP2
not identified in index cases with more than 1 variant
BP1
not applicable
BP7
variant is intronic, so not applicable
BP5
not applicable
PS2
no de novo occurrence
PS4
Variant does not meet PM2 and is identified in 1 case with Simon-Broome criteria of possible FH from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière), France. Need at least 2 unrelated index cases, and also does not meet PM2, so PS4_Supporting is not met.
PS3
no published functional studies
PS1
variant is not missense, so not applicable
Curation History
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