Genetic Variant NM_000078.3:c.1168G>C (chr16-56981179-G-C) – ACMG Classification: Benign (-20 pts)

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.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:4

Conservation

PhyloP100: 1.23

Publications

108 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: Labcorp Genetics (formerly Invitae), Orphanet

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=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 VariationId is 319993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0707 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.1168G>C	p.Ala390Pro	missense	Exon 12 of 16	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.988G>C	p.Ala330Pro	missense	Exon 11 of 15	NP_001273014.1	A0A0S2Z3I8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CETP	ENST00000200676.8	TSL:1 MANE Select	c.1168G>C	p.Ala390Pro	missense	Exon 12 of 16	ENSP00000200676.3	P11597-1
CETP	ENST00000379780.6	TSL:1	c.988G>C	p.Ala330Pro	missense	Exon 11 of 15	ENSP00000369106.2	P11597-2
CETP	ENST00000858282.1		c.1276G>C	p.Ala426Pro	missense	Exon 13 of 17	ENSP00000528341.1

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

GnomAD2 exomes

AF:

0.0516

AC:

12973

AN:

251466

AF XY:

0.0519

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 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

African (AFR)

AF:

0.00714

AC:

239

AN:

33464

American (AMR)

AF:

0.104

AC:

4630

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0137

AC:

358

AN:

26130

East Asian (EAS)

AF:

0.00219

AC:

AN:

39696

South Asian (SAS)

AF:

0.0773

AC:

6668

AN:

86228

European-Finnish (FIN)

AF:

0.0241

AC:

1286

AN:

53388

Middle Eastern (MID)

AF:

0.0284

AC:

164

AN:

5766

European-Non Finnish (NFE)

AF:

0.0533

AC:

59209

AN:

1110964

Other (OTH)

AF:

0.0450

AC:

2718

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

3536

7073

10609

14146

17682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2270

4540

6810

9080

11350

<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:

0.0378

AC:

5759

AN:

152306

Hom.:

177

Cov.:

AF XY:

0.0369

AC XY:

2750

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0113

AC:

471

AN:

41568

American (AMR)

AF:

0.0743

AC:

1137

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0158

AC:

AN:

3472

East Asian (EAS)

AF:

0.00771

AC:

AN:

5186

South Asian (SAS)

AF:

0.0715

AC:

345

AN:

4822

European-Finnish (FIN)

AF:

0.0196

AC:

208

AN:

10622

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0501

AC:

3409

AN:

68014

Other (OTH)

AF:

0.0317

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

276

552

829

1105

1381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0430

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hyperalphalipoproteinemia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

Eigen

Benign

0.18

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

1.2

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.14

Sift

Uncertain

0.027

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.25

MPC

0.68

ClinPred

0.019

GERP RS

2.9

Varity_R

0.84

gMVP

0.66

Mutation Taster

=83/17

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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