rs17231520

Positions:

• chr16-56961915-G-A

Variant summary

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

The 16-56961915-G-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00456 in 1,212,584 control chromosomes in the GnomAD database, including 169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (115 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (54 hom.)
• Consequence: CETP NM_000078.3 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0440

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-56961915-G-A is Benign according to our data. Variant chr16-56961915-G-A is described in ClinVar as [Benign]. Clinvar id is 369115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CETP	NM_000078.3			upstream_gene_variant		ENST00000200676.8
CETP	NM_001286085.2			upstream_gene_variant
CETP	XM_006721124.4			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8			upstream_gene_variant		1	NM_000078.3	P1
CETP	ENST00000379780.6			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3047 AN: 152080 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00233 AC: 2470 AN: 1060386 Hom.: 54 Cov.: 14 AF XY: 0.00200 AC XY: 1091 AN XY: 545364

Gnomad4 AFR exome AF: 0.0631

Gnomad4 AMR exome AF: 0.00496

Gnomad4 ASJ exome AF: 0.00170

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000231

Gnomad4 FIN exome AF: 0.0000198

Gnomad4 NFE exome AF: 0.000407

Gnomad4 OTH exome AF: 0.00536

GnomAD4 genome AF: 0.0201 AC: 3065 AN: 152198 Hom.: 115 Cov.: 32 AF XY: 0.0202 AC XY: 1504 AN XY: 74410

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0124 Hom.: 16

Bravo AF: 0.0230

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hyperalphalipoproteinemia 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 17, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 21, 2019

This variant is associated with the following publications: (PMID: 15324321) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.76

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: rs17231520; hg19: chr16-56995827;