rs2228667

Positions:

• chr16-56983367-G-A
• chr16-56983367-G-C
• chr16-56983367-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000078.3(CETP):​c.1363G>A​(p.Val455Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,614,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V455L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: CETP NM_000078.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.21

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.045701027).
• BP6: Variant 16-56983367-G-A is Benign according to our data. Variant chr16-56983367-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1546097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56983367-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CETP	NM_000078.3	c.1363G>A	p.Val455Met	missense_variant	15/16	ENST00000200676.8
CETP	NM_001286085.2	c.1183G>A	p.Val395Met	missense_variant	14/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8	c.1363G>A	p.Val455Met	missense_variant	15/16	1	NM_000078.3	P1
CETP	ENST00000379780.6	c.1183G>A	p.Val395Met	missense_variant	14/15	1
CETP	ENST00000566128.1	c.1168G>A	p.Val390Met	missense_variant	15/16	5
CETP	ENST00000650358.1	n.1761G>A		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000699

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000835 AC: 21 AN: 251428 Hom.: 0 AF XY: 0.0000515 AC XY: 7 AN XY: 135886

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000499 AC: 73 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23 AN XY: 727244

Gnomad4 AFR exome AF: 0.000836

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000270

Gnomad4 OTH exome AF: 0.000132

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152356 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74502

Gnomad4 AFR AF: 0.000745

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000468 Hom.: 0

Bravo AF: 0.000230

ESP6500AA AF: 0.000682 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N;.;.
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.46	N;N;N
REVEL	Benign	0.039
Sift	Uncertain	0.015	D;D;D
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.83	P;B;.
Vest4		0.18
MVP		0.26
MPC		0.18
ClinPred		0.027	T
GERP RS		3.2
Varity_R		0.11
gMVP		0.29

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: rs2228667; hg19: chr16-57017279;