rs158478

chr16-56973822-A-Cchr16-56973822-A-Gchr16-56973822-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.930+312A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,054 control chromosomes in the GnomAD database, including 17,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.46 (17023 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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=-0.94).
• BP6: Variant 16-56973822-A-C is Benign according to our data. Variant chr16-56973822-A-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CETP	NM_000078.3	c.930+312A>C		intron_variant		ENST00000200676.8
CETP	NM_001286085.2	c.751-1279A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8	c.930+312A>C		intron_variant		1	NM_000078.3	P1
CETP	ENST00000379780.6	c.751-1279A>C		intron_variant		1
CETP	ENST00000566128.1	c.735+312A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70398 AN: 151936 Hom.: 17013 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.463 AC: 70427 AN: 152054 Hom.: 17023 Cov.: 33 AF XY: 0.462 AC XY: 34306 AN XY: 74330

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.513

Alfa AF: 0.348 Hom.: 935

Bravo AF: 0.450

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	-0.94
Cadd	Benign	4.1
Dann	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs158478; hg19: chr16-57007734;