16-56974315-G-A

Position:

• chr16-56974315-G-A

Variant summary

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

The NM_000078.3(CETP):​c.931-786G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,108 control chromosomes in the GnomAD database, including 46,811 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 0.77 (46811 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.931-786G>A		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.751-786G>A		intron_variant			NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.931-786G>A		intron_variant		1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.751-786G>A		intron_variant		1		ENSP00000369106.2
CETP	ENST00000566128.1	c.736-786G>A		intron_variant		5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117804 AN: 151990 Hom.: 46794 Cov.: 33

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.775 AC: 117864 AN: 152108 Hom.: 46811 Cov.: 33 AF XY: 0.770 AC XY: 57310 AN XY: 74386

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.806

Alfa AF: 0.824 Hom.: 6500

Bravo AF: 0.757

Asia WGS AF: 0.693 AC: 2409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.53

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: rs158480; hg19: chr16-57008227;