16-56976029-T-C

Variant names:

• chr16-56976029-T-C
• rs289719
• NM_000078.3:c.981+878T>C

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+878T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,666 control chromosomes in the GnomAD database, including 33,044 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 0.66 (33044 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 24 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.981+878T>C		intron_variant	Intron 10 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.801+878T>C		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+878T>C		intron_variant	Intron 10 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.801+878T>C		intron_variant	Intron 9 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.786+878T>C		intron_variant	Intron 10 of 15	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99486 AN: 151548 Hom.: 33015 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.656 AC: 99563 AN: 151666 Hom.: 33044 Cov.: 32 AF XY: 0.655 AC XY: 48530 AN XY: 74124

African (AFR) AF: 0.595 AC: 24602 AN: 41368

American (AMR) AF: 0.716 AC: 10919 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2045 AN: 3456

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

South Asian (SAS) AF: 0.576 AC: 2775 AN: 4818

European-Finnish (FIN) AF: 0.654 AC: 6862 AN: 10500

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

European-Non Finnish (NFE) AF: 0.690 AC: 46787 AN: 67834

Other (OTH) AF: 0.665 AC: 1404 AN: 2110

Alfa AF: 0.670 Hom.: 4260

Bravo AF: 0.659

Asia WGS AF: 0.615 AC: 2139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.0
DANN	Benign	0.48
PhyloP100		0.032
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: rs289719; hg19: chr16-57009941;