dbSNP rs11076174: CETP:c.234-152T>C (chr16-56969234-T-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.234-152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 996,324 control chromosomes in the GnomAD database, including 4,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 834 hom., cov: 31)

Exomes 𝑓: 0.085 ( 3266 hom. )

Consequence

CETP
NM_000078.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0200

Publications

26 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 (BayesDel_noAF=-0.95).

BP6

Variant 16-56969234-T-C is Benign according to our data. Variant chr16-56969234-T-C is described in ClinVar as Benign. ClinVar VariationId is 1182498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CETP	NM_000078.3 link	c.234-152T>C	intron_variant	Intron 2 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2 link	c.234-152T>C	intron_variant	Intron 2 of 14		NP_001273014.1
CETP	XM_006721124.4 link	c.234-152T>C	intron_variant	Intron 2 of 8		XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CETP	ENST00000200676.8 link	c.234-152T>C	intron_variant	Intron 2 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6 link	c.234-152T>C	intron_variant	Intron 2 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1 link	c.39-152T>C	intron_variant	Intron 2 of 15	5		ENSP00000456276.1
CETP	ENST00000569082.1 link	n.232-152T>C	intron_variant	Intron 2 of 8	5

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15404

AN:

152024

Hom.:

832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0889

Gnomad ASJ

AF:

0.0971

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.0578

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0850

Gnomad OTH

AF:

0.106

GnomAD4 exome

AF:

0.0846

AC:

71435

AN:

844182

Hom.:

3266

AF XY:

0.0831

AC XY:

36861

AN XY:

443664

show subpopulations

African (AFR)

AF:

0.134

AC:

2891

AN:

21590

American (AMR)

AF:

0.0850

AC:

3692

AN:

43426

Ashkenazi Jewish (ASJ)

AF:

0.0974

AC:

2146

AN:

22042

East Asian (EAS)

AF:

0.0884

AC:

3257

AN:

36858

South Asian (SAS)

AF:

0.0584

AC:

4271

AN:

73160

European-Finnish (FIN)

AF:

0.110

AC:

4537

AN:

41060

Middle Eastern (MID)

AF:

0.0894

AC:

267

AN:

2988

European-Non Finnish (NFE)

AF:

0.0829

AC:

46669

AN:

562848

Other (OTH)

AF:

0.0921

AC:

3705

AN:

40210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3667

7335

11002

14670

18337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1128

2256

3384

4512

5640

<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:

0.101

AC:

15425

AN:

152142

Hom.:

834

Cov.:

AF XY:

0.102

AC XY:

7608

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.135

AC:

5595

AN:

41490

American (AMR)

AF:

0.0890

AC:

1361

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0971

AC:

337

AN:

3470

East Asian (EAS)

AF:

0.102

AC:

528

AN:

5164

South Asian (SAS)

AF:

0.0577

AC:

278

AN:

4822

European-Finnish (FIN)

AF:

0.120

AC:

1275

AN:

10594

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0850

AC:

5781

AN:

67994

Other (OTH)

AF:

0.106

AC:

223

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

679

1358

2037

2716

3395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<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:

0.0877

Hom.:

1348

Bravo

AF:

0.102

Asia WGS

AF:

0.0870

AC:

302

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.5

(source)

DANN

Benign

0.51

PhyloP100

-0.020

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over