chr16-56964660-G-C

Variant names:

• chr16-56964660-G-C
• rs9929488
• NM_000078.3:c.233+1536G>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.233+1536G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,788 control chromosomes in the GnomAD database, including 7,414 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 0.30 (7414 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 28 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 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.233+1536G>C		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.233+1536G>C		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.233+1536G>C		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.233+1536G>C		intron	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.38+1536G>C		intron	N/A	ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46114 AN: 151670 Hom.: 7407 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.304 AC: 46151 AN: 151788 Hom.: 7414 Cov.: 32 AF XY: 0.301 AC XY: 22359 AN XY: 74182

African (AFR) AF: 0.405 AC: 16793 AN: 41440

American (AMR) AF: 0.291 AC: 4442 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1019 AN: 3468

East Asian (EAS) AF: 0.159 AC: 799 AN: 5018

South Asian (SAS) AF: 0.306 AC: 1476 AN: 4822

European-Finnish (FIN) AF: 0.254 AC: 2673 AN: 10506

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18061 AN: 67944

Other (OTH) AF: 0.302 AC: 635 AN: 2106

Alfa AF: 0.298 Hom.: 633

Bravo AF: 0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.11
DANN	Benign	0.45
PhyloP100		-1.1
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: rs9929488; hg19: chr16-56998572;