rs12597002

Variant names:

• chr16-56968492-C-A
• rs12597002
• NM_000078.3:c.234-894C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000078.3(CETP):​c.234-894C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,034 control chromosomes in the GnomAD database, including 5,288 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5288 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763
• Publications: 30 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.234-894C>A		intron_variant	Intron 2 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.234-894C>A		intron_variant	Intron 2 of 14		NP_001273014.1
CETP	XM_006721124.4	c.234-894C>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.234-894C>A		intron_variant	Intron 2 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.234-894C>A		intron_variant	Intron 2 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.39-894C>A		intron_variant	Intron 2 of 15	5		ENSP00000456276.1
CETP	ENST00000569082.1	n.232-894C>A		intron_variant	Intron 2 of 8	5

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37919 AN: 151914 Hom.: 5287 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.249 AC: 37925 AN: 152034 Hom.: 5288 Cov.: 32 AF XY: 0.249 AC XY: 18542 AN XY: 74318

African (AFR) AF: 0.128 AC: 5301 AN: 41486

American (AMR) AF: 0.277 AC: 4231 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2082 AN: 5174

South Asian (SAS) AF: 0.210 AC: 1013 AN: 4814

European-Finnish (FIN) AF: 0.304 AC: 3210 AN: 10552

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.295 AC: 20067 AN: 67962

Other (OTH) AF: 0.279 AC: 590 AN: 2114

Alfa AF: 0.286 Hom.: 17908

Bravo AF: 0.245

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.77
DANN	Benign	0.67
PhyloP100		-0.76
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: rs12597002; hg19: chr16-57002404;