rs1800777

Positions:

chr16-56983407-G-A

Variant summary

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

The NM_000078.3(CETP):c.1403G>A(p.Arg468Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 1,613,998 control chromosomes in the GnomAD database, including 1,371 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 0.028 ( 112 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1259 hom. )

Consequence

CETP
NM_000078.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.358

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=0.0024715066).

BP6

Variant 16-56983407-G-A is Benign according to our data. Variant chr16-56983407-G-A is described in ClinVar as [Benign]. Clinvar id is 319999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56983407-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3 linkuse as main transcript	c.1403G>A	p.Arg468Gln	missense_variant	15/16	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2 linkuse as main transcript	c.1223G>A	p.Arg408Gln	missense_variant	14/15		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8 linkuse as main transcript	c.1403G>A	p.Arg468Gln	missense_variant	15/16	1	NM_000078.3	ENSP00000200676	P1	P11597-1
CETP	ENST00000379780.6 linkuse as main transcript	c.1223G>A	p.Arg408Gln	missense_variant	14/15	1		ENSP00000369106		P11597-2
CETP	ENST00000566128.1 linkuse as main transcript	c.1208G>A	p.Arg403Gln	missense_variant	15/16	5		ENSP00000456276
CETP	ENST00000650358.1 linkuse as main transcript			downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4291

AN:

152184

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00832

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0704

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0317

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0359

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0374

AC:

9399

AN:

251464

Hom.:

336

AF XY:

0.0356

AC XY:

4833

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00584

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.00952

Gnomad EAS exome

AF:

0.00136

Gnomad SAS exome

AF:

0.0330

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.0358

Gnomad OTH exome

AF:

0.0288

GnomAD4 exome

AF:

0.0362

AC:

52864

AN:

1461696

Hom.:

1259

Cov.:

AF XY:

0.0357

AC XY:

25955

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00553

Gnomad4 AMR exome

AF:

0.0997

Gnomad4 ASJ exome

AF:

0.0100

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.0335

Gnomad4 FIN exome

AF:

0.0169

Gnomad4 NFE exome

AF:

0.0380

Gnomad4 OTH exome

AF:

0.0302

GnomAD4 genome

AF:

0.0282

AC:

4297

AN:

152302

Hom.:

112

Cov.:

AF XY:

0.0277

AC XY:

2063

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00830

Gnomad4 AMR

AF:

0.0706

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0323

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.0359

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0331

Hom.:

129

Bravo

AF:

0.0312

TwinsUK

AF:

0.0267

AC:

ALSPAC

AF:

0.0392

AC:

151

ESP6500AA

AF:

0.00842

AC:

ESP6500EA

AF:

0.0388

AC:

334

ExAC

AF:

0.0352

AC:

4279

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0328

EpiControl

AF:

0.0360

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 25, 2019	This variant is associated with the following publications: (PMID: 24503134, 9253518, 28008009, 27060904, 29987113) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Hyperalphalipoproteinemia 1

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.30

DANN

Benign

0.53

DEOGEN2

Benign

0.11

T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.73

T;T;T

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.28

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.24

N;N;N

REVEL

Benign

0.012

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.93

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.036

MPC

0.15

ClinPred

0.0026

GERP RS

-5.3

Varity_R

0.046

gMVP

0.33

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

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