16-56983850-C-T

Variant names:

• chr16-56983850-C-T
• rs289742
• NM_000078.3:c.*184C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000078.3(CETP):​c.*184C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CETP NM_000078.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 25 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.*184C>T		downstream_gene_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.*184C>T		downstream_gene_variant			NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.*184C>T		downstream_gene_variant		1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.*184C>T		downstream_gene_variant		1		ENSP00000369106.2
CETP	ENST00000566128.1	c.*184C>T		downstream_gene_variant		5		ENSP00000456276.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 506518 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 273298

African (AFR) AF: 0.00 AC: 0 AN: 14604

American (AMR) AF: 0.00 AC: 0 AN: 32706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17852

East Asian (EAS) AF: 0.00 AC: 0 AN: 29036

South Asian (SAS) AF: 0.00 AC: 0 AN: 60006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2438

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 291216

Other (OTH) AF: 0.00 AC: 0 AN: 27668

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.78
PhyloP100		0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs289742; hg19: chr16-57017762;