16-56976020-C-T

Variant names:

• chr16-56976020-C-T
• rs289718
• NM_000078.3:c.981+869C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000078.3(CETP):​c.981+869C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,676 control chromosomes in the GnomAD database, including 31,622 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31622 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 12 publications found

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]

CETP Gene-Disease associations (from GenCC):

• cholesterol-ester transfer protein deficiency

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.981+869C>T		intron_variant	Intron 10 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.801+869C>T		intron_variant	Intron 9 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.981+869C>T		intron_variant	Intron 10 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.801+869C>T		intron_variant	Intron 9 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.786+869C>T		intron_variant	Intron 10 of 15	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97044 AN: 151558 Hom.: 31598 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.640 AC: 97115 AN: 151676 Hom.: 31622 Cov.: 32 AF XY: 0.639 AC XY: 47400 AN XY: 74142

African (AFR) AF: 0.539 AC: 22294 AN: 41366

American (AMR) AF: 0.709 AC: 10817 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2049 AN: 3464

East Asian (EAS) AF: 0.685 AC: 3519 AN: 5136

South Asian (SAS) AF: 0.576 AC: 2776 AN: 4820

European-Finnish (FIN) AF: 0.653 AC: 6864 AN: 10506

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46768 AN: 67822

Other (OTH) AF: 0.651 AC: 1374 AN: 2110

Alfa AF: 0.651 Hom.: 26379

Bravo AF: 0.641

Asia WGS AF: 0.611 AC: 2127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.74
DANN	Benign	0.68
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs289718; hg19: chr16-57009932;