NM_000078.3:c.1264G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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:8O:1

Conservation

PhyloP100: -2.36

Publications

336 publications found

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 Gene-Disease associations (from GenCC):

cholesterol-ester transfer protein deficiency
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

CETP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 17525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.1264G>A	p.Val422Ile	missense	Exon 14 of 16	NP_000069.2
	CETP	NM_001286085.2		c.1084G>A	p.Val362Ile	missense	Exon 13 of 15	NP_001273014.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CETP	ENST00000200676.8	TSL:1 MANE Select	c.1264G>A	p.Val422Ile	missense	Exon 14 of 16	ENSP00000200676.3
CETP	ENST00000379780.6	TSL:1	c.1084G>A	p.Val362Ile	missense	Exon 13 of 15	ENSP00000369106.2
CETP	ENST00000858282.1		c.1372G>A	p.Val458Ile	missense	Exon 15 of 17	ENSP00000528341.1

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

GnomAD2 exomes

AF:

0.619

AC:

155510

AN:

251372

AF XY:

0.624

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 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

African (AFR)

AF:

0.411

AC:

13748

AN:

33472

American (AMR)

AF:

0.592

AC:

26479

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

15388

AN:

26134

East Asian (EAS)

AF:

0.520

AC:

20651

AN:

39698

South Asian (SAS)

AF:

0.569

AC:

49111

AN:

86244

European-Finnish (FIN)

AF:

0.617

AC:

32963

AN:

53402

Middle Eastern (MID)

AF:

0.582

AC:

3353

AN:

5766

European-Non Finnish (NFE)

AF:

0.685

AC:

761377

AN:

1111626

Other (OTH)

AF:

0.638

AC:

38531

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

18644

37288

55933

74577

93221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19326

38652

57978

77304

96630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.590

AC:

89617

AN:

151952

Hom.:

27578

Cov.:

AF XY:

0.586

AC XY:

43572

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.425

AC:

17582

AN:

41418

American (AMR)

AF:

0.627

AC:

9575

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

2032

AN:

3472

East Asian (EAS)

AF:

0.555

AC:

2864

AN:

5156

South Asian (SAS)

AF:

0.563

AC:

2704

AN:

4802

European-Finnish (FIN)

AF:

0.622

AC:

6557

AN:

10548

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.683

AC:

46403

AN:

67966

Other (OTH)

AF:

0.619

AC:

1307

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1761

3522

5284

7045

8806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.650

Hom.:

152656

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hyperalphalipoproteinemia 1 (2)

not specified (2)

Coronary artery disorder (1)

High density lipoprotein cholesterol level quantitative trait locus 10 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0010

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.070

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0000036

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.57

PhyloP100

-2.4

PrimateAI

Benign

0.29

PROVEAN

Benign

0.52

REVEL

Benign

0.013

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.028

MPC

0.11

ClinPred

0.0086

GERP RS

-6.7

Varity_R

0.017

gMVP

0.088

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over