dbSNP rs2303789: CETP:c.981+132T>G (chr16-56975283-T-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.981+132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 783,678 control chromosomes in the GnomAD database, including 769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 189 hom., cov: 32)

Exomes 𝑓: 0.019 ( 580 hom. )

Consequence

CETP
NM_000078.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.582

Publications

2 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=-0.98).

BP6

Variant 16-56975283-T-G is Benign according to our data. Variant chr16-56975283-T-G is described in ClinVar as Benign. ClinVar VariationId is 1291729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3 link	c.981+132T>G		intron_variant	Intron 10 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2 link	c.801+132T>G		intron_variant	Intron 9 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CETP	ENST00000200676.8 link	c.981+132T>G	intron_variant	Intron 10 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6 link	c.801+132T>G	intron_variant	Intron 9 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1 link	c.786+132T>G	intron_variant	Intron 10 of 15	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes

AF:

0.0335

AC:

5098

AN:

152136

Hom.:

186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0670

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0748

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.0290

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.0302

GnomAD4 exome

AF:

0.0193

AC:

12170

AN:

631424

Hom.:

580

AF XY:

0.0187

AC XY:

6205

AN XY:

332704

show subpopulations

African (AFR)

AF:

0.0669

AC:

1141

AN:

17060

American (AMR)

AF:

0.104

AC:

3329

AN:

32072

Ashkenazi Jewish (ASJ)

AF:

0.000563

AC:

AN:

17766

East Asian (EAS)

AF:

0.123

AC:

3992

AN:

32524

South Asian (SAS)

AF:

0.0277

AC:

1663

AN:

60134

European-Finnish (FIN)

AF:

0.0140

AC:

610

AN:

43420

Middle Eastern (MID)

AF:

0.00594

AC:

AN:

4042

European-Non Finnish (NFE)

AF:

0.00187

AC:

734

AN:

391754

Other (OTH)

AF:

0.0204

AC:

667

AN:

32652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

567

1134

1701

2268

2835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<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:

0.0336

AC:

5121

AN:

152254

Hom.:

189

Cov.:

AF XY:

0.0355

AC XY:

2646

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0671

AC:

2786

AN:

41530

American (AMR)

AF:

0.0754

AC:

1153

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.133

AC:

690

AN:

5184

South Asian (SAS)

AF:

0.0290

AC:

140

AN:

4828

European-Finnish (FIN)

AF:

0.0142

AC:

151

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00193

AC:

131

AN:

68022

Other (OTH)

AF:

0.0318

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

240

480

719

959

1199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0202

Hom.:

Bravo

AF:

0.0425

Asia WGS

AF:

0.0810

AC:

279

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

-0.98

CADD

Benign

0.82

(source)

DANN

Benign

0.42

PhyloP100

-0.58

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