16-56981179-G-C

Position:

chr16-56981179-G-C

Variant summary

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

The NM_000078.3(CETP):c.1168G>C(p.Ala390Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0503 in 1,613,012 control chromosomes in the GnomAD database, including 2,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 177 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2363 hom. )

Consequence

CETP
NM_000078.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.23

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=0.002292037).

BP6

Variant 16-56981179-G-C is Benign according to our data. Variant chr16-56981179-G-C is described in ClinVar as [Benign]. Clinvar id is 319993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56981179-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0707 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.1168G>C	p.Ala390Pro	missense_variant	12/16	ENST00000200676.8
CETP	NM_001286085.2 linkuse as main transcript	c.988G>C	p.Ala330Pro	missense_variant	11/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8 linkuse as main transcript	c.1168G>C	p.Ala390Pro	missense_variant	12/16	1	NM_000078.3	P1	P11597-1
CETP	ENST00000379780.6 linkuse as main transcript	c.988G>C	p.Ala330Pro	missense_variant	11/15	1			P11597-2
CETP	ENST00000566128.1 linkuse as main transcript	c.973G>C	p.Ala325Pro	missense_variant	12/16	5
CETP	ENST00000650358.1 linkuse as main transcript	n.1566G>C		non_coding_transcript_exon_variant	2/5

Frequencies

GnomAD3 genomes

AF:

0.0378

AC:

5757

AN:

152188

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0741

Gnomad ASJ

AF:

0.0158

Gnomad EAS

AF:

0.00770

Gnomad SAS

AF:

0.0713

Gnomad FIN

AF:

0.0196

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0502

Gnomad OTH

AF:

0.0320

GnomAD3 exomes

AF:

0.0516

AC:

12973

AN:

251466

Hom.:

506

AF XY:

0.0519

AC XY:

7047

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00806

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.00587

Gnomad SAS exome

AF:

0.0764

Gnomad FIN exome

AF:

0.0231

Gnomad NFE exome

AF:

0.0510

Gnomad OTH exome

AF:

0.0420

GnomAD4 exome

AF:

0.0516

AC:

75359

AN:

1460706

Hom.:

2363

Cov.:

AF XY:

0.0521

AC XY:

37847

AN XY:

726734

show subpopulations

Gnomad4 AFR exome

AF:

0.00714

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.0137

Gnomad4 EAS exome

AF:

0.00219

Gnomad4 SAS exome

AF:

0.0773

Gnomad4 FIN exome

AF:

0.0241

Gnomad4 NFE exome

AF:

0.0533

Gnomad4 OTH exome

AF:

0.0450

GnomAD4 genome

AF:

0.0378

AC:

5759

AN:

152306

Hom.:

177

Cov.:

AF XY:

0.0369

AC XY:

2750

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.0743

Gnomad4 ASJ

AF:

0.0158

Gnomad4 EAS

AF:

0.00771

Gnomad4 SAS

AF:

0.0715

Gnomad4 FIN

AF:

0.0196

Gnomad4 NFE

AF:

0.0501

Gnomad4 OTH

AF:

0.0317

Alfa

AF:

0.0430

Hom.:

123

Bravo

AF:

0.0396

TwinsUK

AF:

0.0461

AC:

171

ALSPAC

AF:

0.0545

AC:

210

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.0523

AC:

450

ExAC

AF:

0.0508

AC:

6171

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

EpiCase

AF:

0.0480

EpiControl

AF:

0.0528

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2018	This variant is associated with the following publications: (PMID: 29987113, 29083407, 27060904, 28008009, 17952847) -
Benign, criteria provided, single submitter	clinical testing	Invitae	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

Uncertain

0.42

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;.;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

0.89

D;D;N

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.7

D;N;D

REVEL

Benign

0.14

Sift

Uncertain

0.027

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.25

MPC

0.68

ClinPred

0.019

GERP RS

2.9

Varity_R

0.84

gMVP

0.66

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