rs289742

Positions:

• chr16-56983850-C-G
• chr16-56983850-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The 16-56983850-C-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 658,144 control chromosomes in the GnomAD database, including 232,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (49781 hom., cov: 31)
  • Exomes 𝑓: 0.85 (183008 hom.)
• Consequence: CETP NM_000078.3 downstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.177

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 16-56983850-C-G is Benign according to our data. Variant chr16-56983850-C-G is described in ClinVar as [Benign]. Clinvar id is 369116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3			downstream_gene_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2			downstream_gene_variant			NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8			downstream_gene_variant		1	NM_000078.3	ENSP00000200676	P1
CETP	ENST00000379780.6			downstream_gene_variant		1		ENSP00000369106
CETP	ENST00000566128.1			downstream_gene_variant		5		ENSP00000456276

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121907 AN: 151946 Hom.: 49744 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.842

GnomAD4 exome AF: 0.848 AC: 429404 AN: 506080 Hom.: 183008 Cov.: 5 AF XY: 0.847 AC XY: 231377 AN XY: 273056

Gnomad4 AFR exome AF: 0.657

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.879

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.806

Gnomad4 FIN exome AF: 0.873

Gnomad4 NFE exome AF: 0.878

Gnomad4 OTH exome AF: 0.845

GnomAD4 genome AF: 0.802 AC: 121998 AN: 152064 Hom.: 49781 Cov.: 31 AF XY: 0.800 AC XY: 59465 AN XY: 74350

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.844

Alfa AF: 0.838 Hom.: 6777

Bravo AF: 0.790

Asia WGS AF: 0.787 AC: 2736 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hyperalphalipoproteinemia 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
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: rs289742; hg19: chr16-57017762;