rs289716

Variant names:

• chr16-56975464-T-A
• rs289716
• NM_000078.3:c.981+313T>A

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+313T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,028 control chromosomes in the GnomAD database, including 30,650 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 0.63 (30650 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.981+313T>A		intron_variant	Intron 10 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.801+313T>A		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+313T>A		intron_variant	Intron 10 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.801+313T>A		intron_variant	Intron 9 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.786+313T>A		intron_variant	Intron 10 of 15	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95621 AN: 151910 Hom.: 30633 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.629 AC: 95680 AN: 152028 Hom.: 30650 Cov.: 32 AF XY: 0.626 AC XY: 46525 AN XY: 74318

African (AFR) AF: 0.550 AC: 22801 AN: 41438

American (AMR) AF: 0.640 AC: 9783 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2047 AN: 3468

East Asian (EAS) AF: 0.554 AC: 2861 AN: 5168

South Asian (SAS) AF: 0.548 AC: 2645 AN: 4828

European-Finnish (FIN) AF: 0.641 AC: 6766 AN: 10560

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

European-Non Finnish (NFE) AF: 0.688 AC: 46775 AN: 67964

Other (OTH) AF: 0.633 AC: 1338 AN: 2114

Alfa AF: 0.658 Hom.: 4111

Bravo AF: 0.624

Asia WGS AF: 0.539 AC: 1877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		-0.37
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: rs289716; hg19: chr16-57009376;