rs158479

Positions:

• chr16-56974136-G-A
• chr16-56974136-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000078.3(CETP):​c.930+626G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,842 control chromosomes in the GnomAD database, including 17,278 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 0.47 (17278 hom., cov: 31)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.930+626G>A		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.751-965G>A		intron_variant			NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.930+626G>A		intron_variant		1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.751-965G>A		intron_variant		1		ENSP00000369106.2
CETP	ENST00000566128.1	c.735+626G>A		intron_variant		5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70802 AN: 151724 Hom.: 17272 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.466 AC: 70828 AN: 151842 Hom.: 17278 Cov.: 31 AF XY: 0.465 AC XY: 34505 AN XY: 74212

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.505

Alfa AF: 0.489 Hom.: 2293

Bravo AF: 0.453

Asia WGS AF: 0.486 AC: 1689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.82

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: rs158479; hg19: chr16-57008048;