rs289717

Positions:

• chr16-56975476-G-A
• chr16-56975476-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000078.3(CETP):​c.981+325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,106 control chromosomes in the GnomAD database, including 7,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.29 (7010 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-56975476-G-A is Benign according to our data. Variant chr16-56975476-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CETP	NM_000078.3	c.981+325G>A		intron_variant		ENST00000200676.8
CETP	NM_001286085.2	c.801+325G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8	c.981+325G>A		intron_variant		1	NM_000078.3	P1
CETP	ENST00000379780.6	c.801+325G>A		intron_variant		1
CETP	ENST00000566128.1	c.786+325G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44338 AN: 151988 Hom.: 7010 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44346 AN: 152106 Hom.: 7010 Cov.: 32 AF XY: 0.291 AC XY: 21626 AN XY: 74360

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.317

Alfa AF: 0.332 Hom.: 13823

Bravo AF: 0.286

Asia WGS AF: 0.319 AC: 1110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.53

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: rs289717; hg19: chr16-57009388;