rs289742

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-56983850-C-G
• chr16-56983850-C-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.*184C>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
• 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: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.*184C>G		downstream_gene_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.*184C>G		downstream_gene_variant			NP_001273014.1

Ensembl

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

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

African (AFR) AF: 0.657 AC: 9588 AN: 14584

American (AMR) AF: 0.800 AC: 26141 AN: 32678

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 15695 AN: 17850

East Asian (EAS) AF: 0.749 AC: 21696 AN: 28978

South Asian (SAS) AF: 0.806 AC: 48364 AN: 59978

European-Finnish (FIN) AF: 0.873 AC: 27041 AN: 30966

Middle Eastern (MID) AF: 0.816 AC: 1987 AN: 2434

European-Non Finnish (NFE) AF: 0.878 AC: 255543 AN: 290980

Other (OTH) AF: 0.845 AC: 23349 AN: 27632

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

African (AFR) AF: 0.652 AC: 26988 AN: 41408

American (AMR) AF: 0.823 AC: 12578 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3059 AN: 3470

East Asian (EAS) AF: 0.787 AC: 4076 AN: 5180

South Asian (SAS) AF: 0.793 AC: 3820 AN: 4818

European-Finnish (FIN) AF: 0.870 AC: 9219 AN: 10594

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.875 AC: 59493 AN: 67988

Other (OTH) AF: 0.844 AC: 1781 AN: 2110

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hyperalphalipoproteinemia 1 Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.45
PhyloP100		0.18
Mutation Taster		=92/8	polymorphism

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;