rs12708980

Variant names:

• chr16-56978467-T-G
• rs12708980
• NM_000078.3:c.1146+212T>G

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.1146+212T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,832 control chromosomes in the GnomAD database, including 9,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (9657 hom., cov: 31)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.449
• Publications: 43 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=-0.84).
• BP6: Variant 16-56978467-T-G is Benign according to our data. Variant chr16-56978467-T-G is described in ClinVar as Benign. ClinVar VariationId is 1278306.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.1146+212T>G		intron_variant	Intron 11 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.966+212T>G		intron_variant	Intron 10 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.1146+212T>G		intron_variant	Intron 11 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.966+212T>G		intron_variant	Intron 10 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.951+212T>G		intron_variant	Intron 11 of 15	5		ENSP00000456276.1
CETP	ENST00000650358.1	n.1544+212T>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53297 AN: 151716 Hom.: 9642 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.351 AC: 53339 AN: 151832 Hom.: 9657 Cov.: 31 AF XY: 0.348 AC XY: 25835 AN XY: 74220

African (AFR) AF: 0.378 AC: 15647 AN: 41348

American (AMR) AF: 0.351 AC: 5353 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1001 AN: 3472

East Asian (EAS) AF: 0.125 AC: 647 AN: 5164

South Asian (SAS) AF: 0.338 AC: 1628 AN: 4818

European-Finnish (FIN) AF: 0.302 AC: 3187 AN: 10548

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24860 AN: 67928

Other (OTH) AF: 0.332 AC: 699 AN: 2108

Alfa AF: 0.358 Hom.: 40146

Bravo AF: 0.354

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 29, 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	-0.84
CADD	Benign	5.7
DANN	Benign	0.68
PhyloP100		0.45
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: rs12708980; hg19: chr16-57012379;