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]

Variant: NM_000527.5(LDLR):c.1586+16G>A

CA034999

431533 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 85e6a99e-028a-471d-ae0b-7fb7b9c85c03
Approved on: 2023-04-28
Published on: 2023-05-01

HGVS expressions

NM_000527.5:c.1586+16G>A
NM_000527.5(LDLR):c.1586+16G>A
NC_000019.10:g.11113778G>A
CM000681.2:g.11113778G>A
NC_000019.9:g.11224454G>A
CM000681.1:g.11224454G>A
NC_000019.8:g.11085454G>A
NG_009060.1:g.29398G>A
ENST00000558518.6:c.1586+16G>A
ENST00000252444.9:n.1840+16G>A
ENST00000455727.6:c.1082+16G>A
ENST00000535915.5:c.1463+16G>A
ENST00000545707.5:c.1205+16G>A
ENST00000557933.5:c.1586+16G>A
ENST00000558013.5:c.1586+16G>A
ENST00000558518.5:c.1586+16G>A
ENST00000559340.1:n.307+16G>A
NM_000527.4:c.1586+16G>A
NM_001195798.1:c.1586+16G>A
NM_001195799.1:c.1463+16G>A
NM_001195800.1:c.1082+16G>A
NM_001195803.1:c.1205+16G>A
NM_001195798.2:c.1586+16G>A
NM_001195799.2:c.1463+16G>A
NM_001195800.2:c.1082+16G>A
NM_001195803.2:c.1205+16G>A
More

Benign

Met criteria codes 2
BP4 BA1
Not Met criteria codes 19
PS2 PS1 PS3 PS4 BP7 BP2 PP3 PP1 PP4 PM5 PM3 PM4 PM1 PM6 PM2 BS2 BS4 BS3 BS1

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.1586+16G>A variant is classified as Benign for Familial Hypercholesterolemia by applying evidence codes (BA1 and BP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: BA1 - FAF = 0.02014 (2.014%) in African/African American exomes (gnomAD v2.1.1), so BA1 is Met. BP4 - No REVEL, splicing evaluation required. Functional data on splicing not available. A) variant not on limits B) C) variant is not exonic Variant is not predicted to alter splicing. --- BP4 is Met.
Met criteria codes
BP4
No REVEL, splicing evaluation required. Functional data on splicing not available. A) variant not on limits B) C) variant is not exonic Variant is not predicted to alter splicing. --- BP4 is Met.
BA1
FAF = 0.02014 (2.014%) in African/African American exomes (gnomAD v2.1.1), so BA1 is Met.
Not Met criteria codes
PS2
de novo occurrence data not reported, so PS2 is Not Met.
PS1
Variant is in a non-coding region, so PS1 is Not Met.
PS3
There are no functional studies reported for this variant, so PS3 is not met.
PS4
Variant does not meet PM2, so PS4 is Not Met.
BP7
Variant is not synonymous, so BP7 is Not Met.
BP2
Not observed in trans with other LP/P variants, so BP2 is Not Met.
PP3
No REVEL, splicing evaluation required. Functional data on splicing not available. A) variant not on limits B) C) variant is not exonic --- PP3 is not met.
PP1
Segregation data not reported, so PP1 is Not Met.
PP4
Variant does not meet PM2, so PP4 is Not Met.
PM5
Variant is in a non-coding region, so PM5 is Not Met.
PM3
Variant does not meet PM2, so PM3 is Not Met.
PM4
Variant does not meet PM2 and is not due to in-frame deletions/insertions, so PM4 is Not Met.
PM1
Variant does not meet PM2. Also is not located in exon 4 or alters a cysteine residues, so PM1 is Not Met.
PM6
de novo occurrence data not reported, so PM6 is Not Met.
PM2
PopMax MAF = 0.02331 (2.331%) in African/African American exomes+genomes (gnomAD v2.1.1), so PM2 is not met.
BS2
No control individuals tested, so BS2 is Not Met.
BS4
Lack of segregation data not reported, so BS4 is Not Met.
BS3
There are no functional studies reported for this variant, so BS3 is not met.
BS1
FAF = 0.02014 (2.014%) in African/African American exomes (gnomAD v2.1.1), so BS1 is not met.
Curation History
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