rs12708974

Variant names:

• chr16-56971638-C-T
• rs12708974
• NM_000078.3:c.658+257C>T

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.658+257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 152,178 control chromosomes in the GnomAD database, including 734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.087 (734 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.586
• Publications: 17 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 16-56971638-C-T is Benign according to our data. Variant chr16-56971638-C-T is described in ClinVar as [Benign]. Clinvar id is 1225266.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.658+257C>T		intron_variant	Intron 7 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.658+257C>T		intron_variant	Intron 7 of 14		NP_001273014.1
CETP	XM_006721124.4	c.658+257C>T		intron_variant	Intron 7 of 8		XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.658+257C>T		intron_variant	Intron 7 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.658+257C>T		intron_variant	Intron 7 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.463+257C>T		intron_variant	Intron 7 of 15	5		ENSP00000456276.1
CETP	ENST00000569082.1	n.760+257C>T		intron_variant	Intron 7 of 8	5

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 13257 AN: 152060 Hom.: 733 Cov.: 32

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0989

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

GnomAD4 genome AF: 0.0871 AC: 13251 AN: 152178 Hom.: 734 Cov.: 32 AF XY: 0.0898 AC XY: 6678 AN XY: 74386

African (AFR) AF: 0.0200 AC: 829 AN: 41524

American (AMR) AF: 0.0689 AC: 1053 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3472

East Asian (EAS) AF: 0.122 AC: 632 AN: 5172

South Asian (SAS) AF: 0.135 AC: 649 AN: 4816

European-Finnish (FIN) AF: 0.129 AC: 1365 AN: 10592

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7900 AN: 67994

Other (OTH) AF: 0.0984 AC: 208 AN: 2114

Alfa AF: 0.106 Hom.: 1542

Bravo AF: 0.0777

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 04, 2018

GeneDx

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	-0.84
CADD	Benign	7.7
DANN	Benign	0.81
PhyloP100		0.59
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: rs12708974; hg19: chr16-57005550;