rs7203984

chr16-56965346-A-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+2222A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,126 control chromosomes in the GnomAD database, including 8,866 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 (8866 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CETP	NM_000078.3	c.233+2222A>C		intron_variant		ENST00000200676.8
CETP	NM_001286085.2	c.233+2222A>C		intron_variant
CETP	XM_006721124.4	c.233+2222A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8	c.233+2222A>C		intron_variant		1	NM_000078.3	P1
CETP	ENST00000379780.6	c.233+2222A>C		intron_variant		1
CETP	ENST00000566128.1	c.38+2222A>C		intron_variant		5
CETP	ENST00000569082.1	n.231+2222A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46289 AN: 152008 Hom.: 8831 Cov.: 33

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.305 AC: 46390 AN: 152126 Hom.: 8866 Cov.: 33 AF XY: 0.304 AC XY: 22637 AN XY: 74382

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.291

Alfa AF: 0.216 Hom.: 2924

Bravo AF: 0.324

Asia WGS AF: 0.275 AC: 954 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.20
Dann	Benign	0.43

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: rs7203984; hg19: chr16-56999258; COSMIC: COSV52364641;