rs121908056
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_000229.2(LCAT):c.972_974delCCT(p.Leu325del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000137 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L324L) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
LCAT
NM_000229.2 disruptive_inframe_deletion
NM_000229.2 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.55
Publications
1 publications found
Genes affected
LCAT (HGNC:6522): (lecithin-cholesterol acyltransferase) This gene encodes the extracellular cholesterol esterifying enzyme, lecithin-cholesterol acyltransferase. The esterification of cholesterol is required for cholesterol transport. Mutations in this gene have been found to cause fish-eye disease as well as LCAT deficiency. [provided by RefSeq, Jul 2008]
LCAT Gene-Disease associations (from GenCC):
- fish eye diseaseInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
- LCAT deficiencyInheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
- Norum diseaseInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000229.2. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 16-67940252-CAGG-C is Pathogenic according to our data. Variant chr16-67940252-CAGG-C is described in ClinVar as [Pathogenic]. Clinvar id is 3672.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LCAT | NM_000229.2 | c.972_974delCCT | p.Leu325del | disruptive_inframe_deletion | Exon 6 of 6 | ENST00000264005.10 | NP_000220.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461538Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727058 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461538
Hom.:
AF XY:
AC XY:
1
AN XY:
727058
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
1
AN:
53082
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1112008
Other (OTH)
AF:
AC:
0
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
31
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Fish-eye disease Pathogenic:1
Jul 01, 1993
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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