rs158480

Variant names:

• chr16-56974315-G-A
• rs158480
• NM_000078.3:c.931-786G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-56974315-G-A
• chr16-56974315-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.931-786G>A		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.751-786G>A		intron	N/A	NP_001273014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	ENST00000200676.8	TSL:1 MANE Select	c.931-786G>A		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.751-786G>A		intron	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.736-786G>A		intron	N/A	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

African (AFR) AF: 0.611 AC: 25315 AN: 41412

American (AMR) AF: 0.751 AC: 11474 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3059 AN: 3472

East Asian (EAS) AF: 0.660 AC: 3418 AN: 5176

South Asian (SAS) AF: 0.715 AC: 3442 AN: 4816

European-Finnish (FIN) AF: 0.856 AC: 9073 AN: 10604

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59395 AN: 68026

Other (OTH) AF: 0.806 AC: 1706 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.53
PhyloP100		-0.58
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: rs158480; hg19: chr16-57008227;