rs1864163

Variant names:

• chr16-56963321-G-A
• rs1864163
• NM_000078.3:c.233+197G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000078.3(CETP):​c.233+197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,998 control chromosomes in the GnomAD database, including 5,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5184 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.768
• Publications: 113 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-56963321-G-A is Benign according to our data. Variant chr16-56963321-G-A is described in ClinVar as Benign. ClinVar VariationId is 1181969.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.233+197G>A		intron_variant	Intron 2 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.233+197G>A		intron_variant	Intron 2 of 14		NP_001273014.1
CETP	XM_006721124.4	c.233+197G>A		intron_variant	Intron 2 of 8		XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.233+197G>A		intron_variant	Intron 2 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.233+197G>A		intron_variant	Intron 2 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.38+197G>A		intron_variant	Intron 2 of 15	5		ENSP00000456276.1
CETP	ENST00000569082.1	n.231+197G>A		intron_variant	Intron 2 of 8	5

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38881 AN: 151880 Hom.: 5174 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.271

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.256 AC: 38910 AN: 151998 Hom.: 5184 Cov.: 32 AF XY: 0.252 AC XY: 18753 AN XY: 74306

African (AFR) AF: 0.286 AC: 11873 AN: 41446

American (AMR) AF: 0.271 AC: 4135 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 733 AN: 3462

East Asian (EAS) AF: 0.130 AC: 671 AN: 5174

South Asian (SAS) AF: 0.215 AC: 1037 AN: 4818

European-Finnish (FIN) AF: 0.195 AC: 2063 AN: 10576

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17541 AN: 67928

Other (OTH) AF: 0.268 AC: 566 AN: 2112

Alfa AF: 0.257 Hom.: 8765

Bravo AF: 0.263

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.54
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1864163; hg19: chr16-56997233;