rs158477

Variant names:

• chr16-56973698-G-A
• rs158477
• NM_000078.3:c.930+188G>A

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.930+188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,064 control chromosomes in the GnomAD database, including 18,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.49 (18642 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.880
• Publications: 9 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=-0.71).
• BP6: Variant 16-56973698-G-A is Benign according to our data. Variant chr16-56973698-G-A is described in ClinVar as Benign. ClinVar VariationId is 1271769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.930+188G>A		intron_variant	Intron 9 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.751-1403G>A		intron_variant	Intron 8 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.930+188G>A		intron_variant	Intron 9 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.751-1403G>A		intron_variant	Intron 8 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.735+188G>A		intron_variant	Intron 9 of 15	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74564 AN: 151944 Hom.: 18633 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.491 AC: 74599 AN: 152064 Hom.: 18642 Cov.: 33 AF XY: 0.488 AC XY: 36299 AN XY: 74336

African (AFR) AF: 0.423 AC: 17563 AN: 41474

American (AMR) AF: 0.445 AC: 6805 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1994 AN: 3466

East Asian (EAS) AF: 0.524 AC: 2712 AN: 5176

South Asian (SAS) AF: 0.431 AC: 2078 AN: 4826

European-Finnish (FIN) AF: 0.561 AC: 5930 AN: 10576

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35809 AN: 67952

Other (OTH) AF: 0.531 AC: 1122 AN: 2114

Alfa AF: 0.506 Hom.: 2420

Bravo AF: 0.479

Asia WGS AF: 0.490 AC: 1704 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Sep 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs158477; hg19: chr16-57007610;