rs289743

Positions:

• chr16-56983884-G-A
• chr16-56983884-G-C
• chr16-56983884-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The variant allele was found at a frequency of 0.66 in 579,088 control chromosomes in the GnomAD database, including 128,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (30025 hom., cov: 31)
  • Exomes 𝑓: 0.68 (98954 hom.)
• Consequence: intergenic_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.72

Genes affected

(HGNC:):

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-56983884-G-A is Benign according to our data. Variant chr16-56983884-G-A is described in ClinVar as [Benign]. Clinvar id is 1282914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.56983884G>A		intergenic_region
CETP	NM_000078.3	c.*218G>A		downstream_gene_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.*218G>A		downstream_gene_variant			NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.*218G>A		downstream_gene_variant		1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.*218G>A		downstream_gene_variant		1		ENSP00000369106.2
CETP	ENST00000566128.1	c.*218G>A		downstream_gene_variant		5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93362 AN: 151828 Hom.: 30002 Cov.: 31

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.676 AC: 288872 AN: 427142 Hom.: 98954 Cov.: 3 AF XY: 0.674 AC XY: 154938 AN XY: 229824

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.710

Gnomad4 ASJ exome AF: 0.602

Gnomad4 EAS exome AF: 0.650

Gnomad4 SAS exome AF: 0.621

Gnomad4 FIN exome AF: 0.662

Gnomad4 NFE exome AF: 0.707

Gnomad4 OTH exome AF: 0.663

GnomAD4 genome AF: 0.615 AC: 93430 AN: 151946 Hom.: 30025 Cov.: 31 AF XY: 0.615 AC XY: 45665 AN XY: 74264

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.654

Alfa AF: 0.545 Hom.: 1598

Bravo AF: 0.609

Asia WGS AF: 0.620 AC: 2158 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.90
CADD	Benign	0.73
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs289743; hg19: chr16-57017796;