rs2303790
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000078.3(CETP):āc.1376A>Gā(p.Asp459Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00105 in 1,614,202 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D459H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000078.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CETP | NM_000078.3 | c.1376A>G | p.Asp459Gly | missense_variant | 15/16 | ENST00000200676.8 | |
CETP | NM_001286085.2 | c.1196A>G | p.Asp399Gly | missense_variant | 14/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CETP | ENST00000200676.8 | c.1376A>G | p.Asp459Gly | missense_variant | 15/16 | 1 | NM_000078.3 | P1 | |
CETP | ENST00000379780.6 | c.1196A>G | p.Asp399Gly | missense_variant | 14/15 | 1 | |||
CETP | ENST00000566128.1 | c.1181A>G | p.Asp394Gly | missense_variant | 15/16 | 5 | |||
CETP | ENST00000650358.1 | n.1774A>G | non_coding_transcript_exon_variant | 5/5 |
Frequencies
GnomAD3 genomes ? AF: 0.00101 AC: 154AN: 152202Hom.: 6 Cov.: 33
GnomAD3 exomes AF: 0.00257 AC: 646AN: 251456Hom.: 8 AF XY: 0.00234 AC XY: 318AN XY: 135908
GnomAD4 exome AF: 0.00106 AC: 1544AN: 1461882Hom.: 21 Cov.: 32 AF XY: 0.00104 AC XY: 755AN XY: 727242
GnomAD4 genome ? AF: 0.00100 AC: 153AN: 152320Hom.: 6 Cov.: 33 AF XY: 0.00121 AC XY: 90AN XY: 74484
ClinVar
Submissions by phenotype
Hyperalphalipoproteinemia 1 Pathogenic:1Benign:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 24, 1995 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2023 | Reported as a common variant in the East Asian population and is associated with increased HDL-C levels; however, this variant is not associated with decreased LDL-C levels and there is no evidence of a cardioprotective effect (Takahashi et al., 1993; Inazu et al., 1994; Thompson et al., 2009; Khovidhunkit et al., 2012; Millwood et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Functional studies demonstrate that this variant leads to a decrease of CETP activity (Takahashi et al., 1993; Thompson et al., 2009); This variant is associated with the following publications: (PMID: 24497850, 28173125, 8408659, 27516387, 18468607, 25525159, 27896098, 7962532, 25629512, 19444232, 26690388, 29083407, 22464213, 21354572, 27659420, 29141072, 9116424, 31180159, 33358712, 20981092, 12482565, 34426522, 7605382, 7989465, 35174233, 34011801) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at