dbSNP rs289742: CETP:c.*184C>G (chr16-56983850-C-G) – 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.*184C>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 658,144 control chromosomes in the GnomAD database, including 232,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 49781 hom., cov: 31)

Exomes 𝑓: 0.85 ( 183008 hom. )

Consequence

CETP
NM_000078.3 downstream_gene

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.177

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 16-56983850-C-G is Benign according to our data. Variant chr16-56983850-C-G is described in ClinVar as [Benign]. Clinvar id is 369116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3 link	c.*184C>G		downstream_gene_variant		ENST00000200676.8	NP_000069.2	P11597-1A0A0S2Z3F6
CETP	NM_001286085.2 link	c.*184C>G		downstream_gene_variant			NP_001273014.1	A0A0S2Z3I8B4DMZ5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CETP	ENST00000200676.8 link	c.*184C>G	downstream_gene_variant	1	NM_000078.3	ENSP00000200676.3	P11597-1
CETP	ENST00000379780.6 link	c.*184C>G	downstream_gene_variant	1		ENSP00000369106.2	P11597-2
CETP	ENST00000566128.1 link	c.*184C>G	downstream_gene_variant	5		ENSP00000456276.1	H3BRJ9

Frequencies

GnomAD3 genomes

AF:

0.802

AC:

121907

AN:

151946

Hom.:

49744

Cov.:

show subpopulations

Gnomad AFR

AF:

0.652

Gnomad AMI

AF:

0.797

Gnomad AMR

AF:

0.823

Gnomad ASJ

AF:

0.882

Gnomad EAS

AF:

0.787

Gnomad SAS

AF:

0.793

Gnomad FIN

AF:

0.870

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.875

Gnomad OTH

AF:

0.842

GnomAD4 exome

AF:

0.848

AC:

429404

AN:

506080

Hom.:

183008

Cov.:

AF XY:

0.847

AC XY:

231377

AN XY:

273056

show subpopulations

Gnomad4 AFR exome

AF:

0.657

AC:

9588

AN:

14584

Gnomad4 AMR exome

AF:

0.800

AC:

26141

AN:

32678

Gnomad4 ASJ exome

AF:

0.879

AC:

15695

AN:

17850

Gnomad4 EAS exome

AF:

0.749

AC:

21696

AN:

28978

Gnomad4 SAS exome

AF:

0.806

AC:

48364

AN:

59978

Gnomad4 FIN exome

AF:

0.873

AC:

27041

AN:

30966

Gnomad4 NFE exome

AF:

0.878

AC:

255543

AN:

290980

Gnomad4 Remaining exome

AF:

0.845

AC:

23349

AN:

27632

Heterozygous variant carriers

3679

7358

11036

14715

18394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

1064

2128

3192

4256

5320

<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:

0.802

AC:

121998

AN:

152064

Hom.:

49781

Cov.:

AF XY:

0.800

AC XY:

59465

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.652

AC:

0.651758

AN:

0.651758

Gnomad4 AMR

AF:

0.823

AC:

0.822629

AN:

0.822629

Gnomad4 ASJ

AF:

0.882

AC:

0.881556

AN:

0.881556

Gnomad4 EAS

AF:

0.787

AC:

0.786873

AN:

0.786873

Gnomad4 SAS

AF:

0.793

AC:

0.79286

AN:

0.79286

Gnomad4 FIN

AF:

0.870

AC:

0.87021

AN:

0.87021

Gnomad4 NFE

AF:

0.875

AC:

0.875051

AN:

0.875051

Gnomad4 OTH

AF:

0.844

AC:

0.844076

AN:

0.844076

Heterozygous variant carriers

1174

2349

3523

4698

5872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.838

Hom.:

6777

Bravo

AF:

0.790

Asia WGS

AF:

0.787

AC:

2736

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hyperalphalipoproteinemia 1

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

-0.94

CADD

Benign

3.6

DANN

Benign

0.45

Mutation Taster

=92/8

polymorphism

Splicing

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