NM_000078.3:c.*218G>C

Variant names:

• chr16-56983884-G-C
• rs289743
• NM_000078.3:c.*218G>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_000078.3(CETP):​c.*218G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 579,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00049 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: CETP NM_000078.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000493 (75/152002) while in subpopulation AFR AF= 0.00164 (68/41428). AF 95% confidence interval is 0.00133. There are 0 homozygotes in gnomad4. There are 33 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.*218G>C		downstream_gene_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.*218G>C		downstream_gene_variant			NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.*218G>C		downstream_gene_variant		1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.*218G>C		downstream_gene_variant		1		ENSP00000369106.2
CETP	ENST00000566128.1	c.*218G>C		downstream_gene_variant		5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.000494 AC: 75 AN: 151884 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000108 AC: 46 AN: 427706 Hom.: 0 Cov.: 3 AF XY: 0.0000826 AC XY: 19 AN XY: 230102

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.000455

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000367

Gnomad4 OTH exome AF: 0.000212

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152002 Hom.: 0 Cov.: 31 AF XY: 0.000444 AC XY: 33 AN XY: 74294

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs289743; hg19: chr16-57017796;