rs12720922

Variant names:

• chr16-56966973-G-A
• rs12720922
• NM_000078.3:c.234-2413G>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.234-2413G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,842 control chromosomes in the GnomAD database, including 4,331 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 0.23 (4331 hom., cov: 30)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857
• Publications: 26 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 (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.234-2413G>A		intron_variant	Intron 2 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.234-2413G>A		intron_variant	Intron 2 of 14		NP_001273014.1
CETP	XM_006721124.4	c.234-2413G>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.234-2413G>A		intron_variant	Intron 2 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.234-2413G>A		intron_variant	Intron 2 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.39-2413G>A		intron_variant	Intron 2 of 15	5		ENSP00000456276.1
CETP	ENST00000569082.1	n.232-2413G>A		intron_variant	Intron 2 of 8	5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34240 AN: 151724 Hom.: 4320 Cov.: 30

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.226 AC: 34287 AN: 151842 Hom.: 4331 Cov.: 30 AF XY: 0.224 AC XY: 16650 AN XY: 74220

African (AFR) AF: 0.335 AC: 13858 AN: 41336

American (AMR) AF: 0.230 AC: 3498 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 518 AN: 3470

East Asian (EAS) AF: 0.129 AC: 665 AN: 5168

South Asian (SAS) AF: 0.200 AC: 962 AN: 4810

European-Finnish (FIN) AF: 0.165 AC: 1742 AN: 10550

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12441 AN: 67964

Other (OTH) AF: 0.217 AC: 456 AN: 2104

Alfa AF: 0.191 Hom.: 6007

Bravo AF: 0.233

Asia WGS AF: 0.179 AC: 623 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	4.2
DANN	Benign	0.66
PhyloP100		-0.86
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: rs12720922; hg19: chr16-57000885;