rs289743

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-56983884-G-A
• chr16-56983884-G-C
• chr16-56983884-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000078.3(CETP):​c.*218G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 579,088 control chromosomes in the GnomAD database, including 128,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (30025 hom., cov: 31)
  • Exomes 𝑓: 0.68 (98954 hom.)
• Consequence: CETP NM_000078.3 downstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.72
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-56983884-G-A is Benign according to our data. Variant chr16-56983884-G-A is described in ClinVar as Benign. ClinVar VariationId is 1282914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.*218G>A		downstream_gene	N/A	NP_000069.2
	CETP	NM_001286085.2		c.*218G>A		downstream_gene	N/A	NP_001273014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	ENST00000200676.8	TSL:1 MANE Select	c.*218G>A		downstream_gene	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.*218G>A		downstream_gene	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.*218G>A		downstream_gene	N/A	ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93362 AN: 151828 Hom.: 30002 Cov.: 31

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.676 AC: 288872 AN: 427142 Hom.: 98954 Cov.: 3 AF XY: 0.674 AC XY: 154938 AN XY: 229824

African (AFR) AF: 0.428 AC: 5440 AN: 12720

American (AMR) AF: 0.710 AC: 20280 AN: 28560

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 8415 AN: 13986

East Asian (EAS) AF: 0.650 AC: 16069 AN: 24720

South Asian (SAS) AF: 0.621 AC: 32828 AN: 52860

European-Finnish (FIN) AF: 0.662 AC: 16103 AN: 24320

Middle Eastern (MID) AF: 0.626 AC: 1165 AN: 1860

European-Non Finnish (NFE) AF: 0.707 AC: 172946 AN: 244550

Other (OTH) AF: 0.663 AC: 15626 AN: 23566

GnomAD4 genome AF: 0.615 AC: 93430 AN: 151946 Hom.: 30025 Cov.: 31 AF XY: 0.615 AC XY: 45665 AN XY: 74264

African (AFR) AF: 0.426 AC: 17648 AN: 41404

American (AMR) AF: 0.703 AC: 10737 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2071 AN: 3472

East Asian (EAS) AF: 0.688 AC: 3565 AN: 5178

South Asian (SAS) AF: 0.610 AC: 2940 AN: 4822

European-Finnish (FIN) AF: 0.659 AC: 6953 AN: 10550

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47453 AN: 67940

Other (OTH) AF: 0.654 AC: 1380 AN: 2110

Alfa AF: 0.545 Hom.: 1598

Bravo AF: 0.609

Asia WGS AF: 0.620 AC: 2158 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.73
DANN	Benign	0.71
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs289743; hg19: chr16-57017796;