rs2303789

chr16-56975283-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000078.3(CETP):c.981+132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 783,678 control chromosomes in the GnomAD database, including 769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (189 hom., cov: 32)
  • Exomes 𝑓: 0.019 (580 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.582

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-56975283-T-G is Benign according to our data. Variant chr16-56975283-T-G is described in ClinVar as [Benign]. Clinvar id is 1291729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CETP	NM_000078.3	c.981+132T>G		intron_variant		ENST00000200676.8
CETP	NM_001286085.2	c.801+132T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8	c.981+132T>G		intron_variant		1	NM_000078.3	P1
CETP	ENST00000379780.6	c.801+132T>G		intron_variant		1
CETP	ENST00000566128.1	c.786+132T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5098 AN: 152136 Hom.: 186 Cov.: 32

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0748

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.0302

GnomAD4 exome AF: 0.0193 AC: 12170 AN: 631424 Hom.: 580 AF XY: 0.0187 AC XY: 6205 AN XY: 332704

Gnomad4 AFR exome AF: 0.0669

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.000563

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.0277

Gnomad4 FIN exome AF: 0.0140

Gnomad4 NFE exome AF: 0.00187

Gnomad4 OTH exome AF: 0.0204

GnomAD4 genome AF: 0.0336 AC: 5121 AN: 152254 Hom.: 189 Cov.: 32 AF XY: 0.0355 AC XY: 2646 AN XY: 74446

Gnomad4 AFR AF: 0.0671

Gnomad4 AMR AF: 0.0754

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.0142

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.0193 Hom.: 13

Bravo AF: 0.0425

Asia WGS AF: 0.0810 AC: 279 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.82
Dann	Benign	0.42

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: rs2303789; hg19: chr16-57009195; COSMIC: COSV52364939; COSMIC: COSV52364939;