rs1801706

chr16-56983750-G-Achr16-56983750-G-Cchr16-56983750-G-T

Variant summary

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

The NM_000078.3(CETP):c.*84G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,303,282 control chromosomes in the GnomAD database, including 20,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2198 hom., cov: 32)
  • Exomes 𝑓: 0.17 (18081 hom.)
• Consequence: CETP NM_000078.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.20

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=-0.9).
• BP6: Variant 16-56983750-G-A is Benign according to our data. Variant chr16-56983750-G-A is described in ClinVar as [Benign]. Clinvar id is 320000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56983750-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CETP	NM_000078.3	c.*84G>A		3_prime_UTR_variant	16/16	ENST00000200676.8
CETP	NM_001286085.2	c.*84G>A		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8	c.*84G>A		3_prime_UTR_variant	16/16	1	NM_000078.3	P1
CETP	ENST00000379780.6	c.*84G>A		3_prime_UTR_variant	15/15	1
CETP	ENST00000566128.1	c.*84G>A		3_prime_UTR_variant	16/16	5

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25083 AN: 152024 Hom.: 2198 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0992

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.174 AC: 199929 AN: 1151140 Hom.: 18081 Cov.: 16 AF XY: 0.175 AC XY: 102613 AN XY: 587044

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.0850

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.165 AC: 25095 AN: 152142 Hom.: 2198 Cov.: 32 AF XY: 0.164 AC XY: 12174 AN XY: 74362

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.0990

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.175

Alfa AF: 0.171 Hom.: 4462

Bravo AF: 0.156

Asia WGS AF: 0.164 AC: 568 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 17, 2018

This variant is associated with the following publications: (PMID: 8830936, 27768712) -

Hyperalphalipoproteinemia 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.026
Dann	Benign	0.47

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: rs1801706; hg19: chr16-57017662;