dbSNP rs891144: CETP:c.982-67C>T (chr16-56978024-C-T) – 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.982-67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 1,578,790 control chromosomes in the GnomAD database, including 2,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 882 hom., cov: 32)

Exomes 𝑓: 0.024 ( 1462 hom. )

Consequence

CETP
NM_000078.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.12

Publications

10 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=-0.9).

BP6

Variant 16-56978024-C-T is Benign according to our data. Variant chr16-56978024-C-T is described in ClinVar as Benign. ClinVar VariationId is 1228339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3 link	c.982-67C>T		intron_variant	Intron 10 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2 link	c.802-67C>T		intron_variant	Intron 9 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CETP	ENST00000200676.8 link	c.982-67C>T	intron_variant	Intron 10 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6 link	c.802-67C>T	intron_variant	Intron 9 of 14	1		ENSP00000369106.2
CETP	ENST00000650358.1 link	n.1313C>T	non_coding_transcript_exon_variant	Exon 1 of 5
CETP	ENST00000566128.1 link	c.787-67C>T	intron_variant	Intron 10 of 15	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes

AF:

0.0719

AC:

10936

AN:

152102

Hom.:

879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0932

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.0164

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.0608

GnomAD4 exome

AF:

0.0237

AC:

33771

AN:

1426570

Hom.:

1462

AF XY:

0.0236

AC XY:

16680

AN XY:

707036

show subpopulations

African (AFR)

AF:

0.190

AC:

6209

AN:

32656

American (AMR)

AF:

0.118

AC:

5010

AN:

42608

Ashkenazi Jewish (ASJ)

AF:

0.00624

AC:

152

AN:

24354

East Asian (EAS)

AF:

0.118

AC:

4651

AN:

39348

South Asian (SAS)

AF:

0.0495

AC:

4084

AN:

82568

European-Finnish (FIN)

AF:

0.0172

AC:

883

AN:

51272

Middle Eastern (MID)

AF:

0.0145

AC:

AN:

4412

European-Non Finnish (NFE)

AF:

0.00991

AC:

10802

AN:

1090526

Other (OTH)

AF:

0.0326

AC:

1916

AN:

58826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1619

3238

4856

6475

8094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

656

1312

1968

2624

3280

<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:

0.0721

AC:

10969

AN:

152220

Hom.:

882

Cov.:

AF XY:

0.0721

AC XY:

5370

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.183

AC:

7613

AN:

41526

American (AMR)

AF:

0.0937

AC:

1432

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3470

East Asian (EAS)

AF:

0.125

AC:

648

AN:

5166

South Asian (SAS)

AF:

0.0532

AC:

257

AN:

4830

European-Finnish (FIN)

AF:

0.0164

AC:

174

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

698

AN:

68012

Other (OTH)

AF:

0.0620

AC:

131

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

460

919

1379

1838

2298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0301

Hom.:

189

Bravo

AF:

0.0851

Asia WGS

AF:

0.0980

AC:

340

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

- -

Apr 08, 2019

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

-0.90

CADD

Benign

0.064

(source)

DANN

Benign

0.59

PhyloP100

-3.1

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