rs5882

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000078.3(CETP):c.1264G>A(p.Val422Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 1,613,398 control chromosomes in the GnomAD database, including 346,892 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27578 hom., cov: 31)

Exomes 𝑓: 0.66 ( 319314 hom. )

Consequence

CETP
NM_000078.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -2.36

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.5843727E-6).

BP6

Variant 16-56982180-G-A is Benign according to our data. Variant chr16-56982180-G-A is described in ClinVar as [Benign]. Clinvar id is 17525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56982180-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CETP	NM_000078.3 linkuse as main transcript	c.1264G>A	p.Val422Ile	missense_variant	14/16	ENST00000200676.8
CETP	NM_001286085.2 linkuse as main transcript	c.1084G>A	p.Val362Ile	missense_variant	13/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8 linkuse as main transcript	c.1264G>A	p.Val422Ile	missense_variant	14/16	1	NM_000078.3	P1	P11597-1
CETP	ENST00000379780.6 linkuse as main transcript	c.1084G>A	p.Val362Ile	missense_variant	13/15	1			P11597-2
CETP	ENST00000566128.1 linkuse as main transcript	c.1069G>A	p.Val357Ile	missense_variant	14/16	5
CETP	ENST00000650358.1 linkuse as main transcript	n.1662G>A		non_coding_transcript_exon_variant	4/5

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89567

AN:

151834

Hom.:

27562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.585

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.620

GnomAD3 exomes

AF:

0.619

AC:

155510

AN:

251372

Hom.:

48877

AF XY:

0.624

AC XY:

84847

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.418

Gnomad AMR exome

AF:

0.586

Gnomad ASJ exome

AF:

0.592

Gnomad EAS exome

AF:

0.554

Gnomad SAS exome

AF:

0.567

Gnomad FIN exome

AF:

0.621

Gnomad NFE exome

AF:

0.684

Gnomad OTH exome

AF:

0.617

GnomAD4 exome

AF:

0.658

AC:

961601

AN:

1461446

Hom.:

319314

Cov.:

AF XY:

0.656

AC XY:

477060

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.411

Gnomad4 AMR exome

AF:

0.592

Gnomad4 ASJ exome

AF:

0.589

Gnomad4 EAS exome

AF:

0.520

Gnomad4 SAS exome

AF:

0.569

Gnomad4 FIN exome

AF:

0.617

Gnomad4 NFE exome

AF:

0.685

Gnomad4 OTH exome

AF:

0.638

GnomAD4 genome

AF:

0.590

AC:

89617

AN:

151952

Hom.:

27578

Cov.:

AF XY:

0.586

AC XY:

43572

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.425

Gnomad4 AMR

AF:

0.627

Gnomad4 ASJ

AF:

0.585

Gnomad4 EAS

AF:

0.555

Gnomad4 SAS

AF:

0.563

Gnomad4 FIN

AF:

0.622

Gnomad4 NFE

AF:

0.683

Gnomad4 OTH

AF:

0.619

Alfa

AF:

0.657

Hom.:

81813

Bravo

AF:

0.580

TwinsUK

AF:

0.687

AC:

2549

ALSPAC

AF:

0.676

AC:

2605

ESP6500AA

AF:

0.415

AC:

1823

ESP6500EA

AF:

0.681

AC:

5860

ExAC

AF:

0.616

AC:

74827

Asia WGS

AF:

0.533

AC:

1857

AN:

3478

EpiCase

AF:

0.682

EpiControl

AF:

0.672

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	This variant is associated with the following publications: (PMID: 10092998, 23977315, 25260850, 22464147, 21767357, 20068209, 14559957, 19242900, 23274582, 22122979) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Hyperalphalipoproteinemia 1

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

Coronary artery disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Rasad Genetic Department, Rasad Pathobiology and Genetic Laboratory

May 12, 2022

- -

High density lipoprotein cholesterol level quantitative trait locus 10

Other:1

association, no assertion criteria provided

literature only

OMIM

Jan 13, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0010

DANN

Benign

0.24

DEOGEN2

Benign

0.070

T;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.50

T;T;T

MetaRNN

Benign

0.0000036

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.57

N;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

0.52

N;N;N

REVEL

Benign

0.013

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.028

MPC

0.11

ClinPred

0.0086

GERP RS

-6.7

Varity_R

0.017

gMVP

0.088

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over