rs12720889

Positions:

• chr16-56978651-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000078.3(CETP):​c.1146+396A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 146,014 control chromosomes in the GnomAD database, including 5,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.27 (5675 hom., cov: 29)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-56978651-A-T is Benign according to our data. Variant chr16-56978651-A-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CETP	NM_000078.3	c.1146+396A>T		intron_variant		ENST00000200676.8
CETP	NM_001286085.2	c.966+396A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8	c.1146+396A>T		intron_variant		1	NM_000078.3	P1
CETP	ENST00000379780.6	c.966+396A>T		intron_variant		1
CETP	ENST00000566128.1	c.951+396A>T		intron_variant		5
CETP	ENST00000650358.1	n.1544+396A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.273 AC: 39796 AN: 145926 Hom.: 5676 Cov.: 29

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.273 AC: 39804 AN: 146014 Hom.: 5675 Cov.: 29 AF XY: 0.275 AC XY: 19513 AN XY: 70892

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.287

Alfa AF: 0.270 Hom.: 521

Bravo AF: 0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs12720889; hg19: chr16-57012563;