rs289741

chr16-56983562-G-Achr16-56983562-G-Cchr16-56983562-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.61 (29951 hom., cov: 32)
  • Exomes 𝑓: 0.68 (339994 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.788

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: 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_single_submitter, 1 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	UniProt
CETP	NM_000078.3	c.1408-30G>A		intron_variant		ENST00000200676.8
CETP	NM_001286085.2	c.1228-30G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8	c.1408-30G>A		intron_variant		1	NM_000078.3	P1
CETP	ENST00000379780.6	c.1228-30G>A		intron_variant		1
CETP	ENST00000566128.1	c.1213-30G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93249 AN: 151896 Hom.: 29926 Cov.: 32

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

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.: 38 AF XY: 0.678 AC XY: 493011 AN XY: 726812

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.: 32 AF XY: 0.614 AC XY: 45607 AN XY: 74292

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

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

Other links and lift over

dbSNP: rs289741; hg19: chr16-57017474;