dbSNP rs9930761: CETP:c.751-51T>C (chr16-56973280-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000078.3(CETP):c.751-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 1,595,658 control chromosomes in the GnomAD database, including 3,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 461 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3126 hom. )

Consequence

CETP
NM_000078.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.605

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 16-56973280-T-C is Benign according to our data. Variant chr16-56973280-T-C is described in ClinVar as [Benign]. Clinvar id is 1297243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56973280-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3 link	c.751-51T>C		intron_variant	Intron 8 of 15	ENST00000200676.8	NP_000069.2	P11597-1A0A0S2Z3F6
CETP	NM_001286085.2 link	c.750+1197T>C		intron_variant	Intron 8 of 14		NP_001273014.1	A0A0S2Z3I8B4DMZ5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CETP	ENST00000200676.8 link	c.751-51T>C	intron_variant	Intron 8 of 15	1	NM_000078.3	ENSP00000200676.3	P11597-1
CETP	ENST00000379780.6 link	c.750+1197T>C	intron_variant	Intron 8 of 14	1		ENSP00000369106.2	P11597-2
CETP	ENST00000566128.1 link	c.556-51T>C	intron_variant	Intron 8 of 15	5		ENSP00000456276.1	H3BRJ9
CETP	ENST00000569082.1 link	n.853-51T>C	intron_variant	Intron 8 of 8	5

Frequencies

GnomAD3 genomes

AF:

0.0716

AC:

10889

AN:

152162

Hom.:

459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.0466

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0599

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0628

Gnomad OTH

AF:

0.0665

GnomAD3 exomes

AF:

0.0594

AC:

14705

AN:

247614

Hom.:

533

AF XY:

0.0596

AC XY:

7995

AN XY:

134196

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.0337

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.000491

Gnomad SAS exome

AF:

0.0576

Gnomad FIN exome

AF:

0.0436

Gnomad NFE exome

AF:

0.0662

Gnomad OTH exome

AF:

0.0724

GnomAD4 exome

AF:

0.0627

AC:

90556

AN:

1443378

Hom.:

3126

Cov.:

AF XY:

0.0627

AC XY:

45035

AN XY:

718822

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.0351

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.000354

Gnomad4 SAS exome

AF:

0.0593

Gnomad4 FIN exome

AF:

0.0479

Gnomad4 NFE exome

AF:

0.0639

Gnomad4 OTH exome

AF:

0.0629

GnomAD4 genome

AF:

0.0716

AC:

10900

AN:

152280

Hom.:

461

Cov.:

AF XY:

0.0677

AC XY:

5037

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.0465

Gnomad4 ASJ

AF:

0.128

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0609

Gnomad4 FIN

AF:

0.0386

Gnomad4 NFE

AF:

0.0628

Gnomad4 OTH

AF:

0.0687

Alfa

AF:

0.0686

Hom.:

742

Bravo

AF:

0.0743

Asia WGS

AF:

0.0360

AC:

125

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

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24393849, 22403620) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.90

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

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