Variant chr16-56983562-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000078.3(CETP):c.1408-30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,612,930 control chromosomes in the GnomAD database, including 369,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.61 ( 29951 hom., cov: 32)

Exomes 𝑓: 0.68 ( 339994 hom. )

Consequence

CETP
NM_000078.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.788

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

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 16-56983562-G-A is Benign according to our data. Variant chr16-56983562-G-A is described in ClinVar as [Benign]. Clinvar id is 1285774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56983562-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3 linkuse as main transcript	c.1408-30G>A		intron_variant		ENST00000200676.8	NP_000069.2	P11597-1A0A0S2Z3F6
CETP	NM_001286085.2 linkuse as main transcript	c.1228-30G>A		intron_variant			NP_001273014.1	A0A0S2Z3I8B4DMZ5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CETP	ENST00000200676.8 linkuse as main transcript	c.1408-30G>A	intron_variant	1	NM_000078.3	ENSP00000200676.3	P11597-1
CETP	ENST00000379780.6 linkuse as main transcript	c.1228-30G>A	intron_variant	1		ENSP00000369106.2	P11597-2
CETP	ENST00000566128.1 linkuse as main transcript	c.1213-30G>A	intron_variant	5		ENSP00000456276.1	H3BRJ9

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93249

AN:

151896

Hom.:

29926

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.689

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.659

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.698

Gnomad OTH

AF:

0.649

GnomAD3 exomes

AF:

0.661

AC:

166087

AN:

251130

Hom.:

55649

AF XY:

0.664

AC XY:

90157

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.420

Gnomad AMR exome

AF:

0.701

Gnomad ASJ exome

AF:

0.596

Gnomad EAS exome

AF:

0.694

Gnomad SAS exome

AF:

0.611

Gnomad FIN exome

AF:

0.658

Gnomad NFE exome

AF:

0.699

Gnomad OTH exome

AF:

0.651

GnomAD4 exome

AF:

0.680

AC:

993571

AN:

1460916

Hom.:

339994

Cov.:

AF XY:

0.678

AC XY:

493011

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.411

Gnomad4 AMR exome

AF:

0.702

Gnomad4 ASJ exome

AF:

0.593

Gnomad4 EAS exome

AF:

0.647

Gnomad4 SAS exome

AF:

0.614

Gnomad4 FIN exome

AF:

0.654

Gnomad4 NFE exome

AF:

0.698

Gnomad4 OTH exome

AF:

0.663

GnomAD4 genome

AF:

0.614

AC:

93318

AN:

152014

Hom.:

29951

Cov.:

AF XY:

0.614

AC XY:

45607

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.425

Gnomad4 AMR

AF:

0.702

Gnomad4 ASJ

AF:

0.591

Gnomad4 EAS

AF:

0.690

Gnomad4 SAS

AF:

0.607

Gnomad4 FIN

AF:

0.659

Gnomad4 NFE

AF:

0.698

Gnomad4 OTH

AF:

0.650

Alfa

AF:

0.658

Hom.:

14889

Bravo

AF:

0.608

Asia WGS

AF:

0.621

AC:

2161

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.79

DANN

Benign

0.83

BranchPoint Hunter

2.0

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