rs9929488

Positions:

• chr16-56964660-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.233+1536G>C		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.233+1536G>C		intron_variant			NP_001273014.1
CETP	XM_006721124.4	c.233+1536G>C		intron_variant			XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.233+1536G>C		intron_variant		1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.233+1536G>C		intron_variant		1		ENSP00000369106.2
CETP	ENST00000566128.1	c.38+1536G>C		intron_variant		5		ENSP00000456276.1
CETP	ENST00000569082.1	n.231+1536G>C		intron_variant		5

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

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.302

Alfa AF: 0.298 Hom.: 633

Bravo AF: 0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.11
DANN	Benign	0.45

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: rs9929488; hg19: chr16-56998572;