dbSNP rs12708980: CETP:c.1146+212T>G (chr16-56978467-T-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000078.3(CETP):c.1146+212T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,832 control chromosomes in the GnomAD database, including 9,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.35 ( 9657 hom., cov: 31)

Consequence

CETP
NM_000078.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.449

Publications

43 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-56978467-T-G is Benign according to our data. Variant chr16-56978467-T-G is described in ClinVar as Benign. ClinVar VariationId is 1278306.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 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.1146+212T>G		intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.966+212T>G		intron	N/A	NP_001273014.1	A0A0S2Z3I8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CETP	ENST00000200676.8	TSL:1 MANE Select	c.1146+212T>G	intron	N/A	ENSP00000200676.3	P11597-1
CETP	ENST00000379780.6	TSL:1	c.966+212T>G	intron	N/A	ENSP00000369106.2	P11597-2
CETP	ENST00000858282.1		c.1254+212T>G	intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53297

AN:

151716

Hom.:

9642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.378

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.336

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.351

AC:

53339

AN:

151832

Hom.:

9657

Cov.:

AF XY:

0.348

AC XY:

25835

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.378

AC:

15647

AN:

41348

American (AMR)

AF:

0.351

AC:

5353

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

1001

AN:

3472

East Asian (EAS)

AF:

0.125

AC:

647

AN:

5164

South Asian (SAS)

AF:

0.338

AC:

1628

AN:

4818

European-Finnish (FIN)

AF:

0.302

AC:

3187

AN:

10548

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.366

AC:

24860

AN:

67928

Other (OTH)

AF:

0.332

AC:

699

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1792

3584

5375

7167

8959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<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:

0.358

Hom.:

40146

Bravo

AF:

0.354

Asia WGS

AF:

0.232

AC:

806

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.7

(source)

DANN

Benign

0.68

PhyloP100

0.45

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over