16-56982180-G-C

Position:

• chr16-56982180-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000078.3(CETP):​c.1264G>C​(p.Val422Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V422I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CETP NM_000078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36

Genes affected

CETP (HGNC:1869): (cholesteryl ester transfer protein) The protein encoded by this gene is found in plasma, where it is involved in the transfer of cholesteryl ester from high density lipoprotein (HDL) to other lipoproteins. Defects in this gene are a cause of hyperalphalipoproteinemia 1 (HALP1). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

CETP (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049870342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.1264G>C	p.Val422Leu	missense_variant	14/16	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.1084G>C	p.Val362Leu	missense_variant	13/15		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.1264G>C	p.Val422Leu	missense_variant	14/16	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.1084G>C	p.Val362Leu	missense_variant	13/15	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.1069G>C	p.Val357Leu	missense_variant	14/16	5		ENSP00000456276.1
CETP	ENST00000650358.1	n.1662G>C		non_coding_transcript_exon_variant	4/5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0010
DANN	Benign	0.33
DEOGEN2	Benign	0.070	T;.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.050	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.83	N;N;N
REVEL	Benign	0.0050
Sift	Benign	0.63	T;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.12
MutPred		0.35		Gain of disorder (P = 0.1909);.;.;
MVP		0.067
MPC		0.13
ClinPred		0.034	T
GERP RS		-6.7
Varity_R		0.028
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5882; hg19: chr16-57016092;