rs11076174

Positions:

• chr16-56969234-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000200676.8(CETP):​c.234-152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 996,324 control chromosomes in the GnomAD database, including 4,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (834 hom., cov: 31)
  • Exomes 𝑓: 0.085 (3266 hom.)
• Consequence: CETP ENST00000200676.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0200

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 16-56969234-T-C is Benign according to our data. Variant chr16-56969234-T-C is described in ClinVar as [Benign]. Clinvar id is 1182498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.234-152T>C		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.234-152T>C		intron_variant			NP_001273014.1
CETP	XM_006721124.4	c.234-152T>C		intron_variant			XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.234-152T>C		intron_variant		1	NM_000078.3	ENSP00000200676	P1
CETP	ENST00000379780.6	c.234-152T>C		intron_variant		1		ENSP00000369106
CETP	ENST00000566128.1	c.39-152T>C		intron_variant		5		ENSP00000456276
CETP	ENST00000569082.1	n.232-152T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15404 AN: 152024 Hom.: 832 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0889

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0578

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0850

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0846 AC: 71435 AN: 844182 Hom.: 3266 AF XY: 0.0831 AC XY: 36861 AN XY: 443664

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.0850

Gnomad4 ASJ exome AF: 0.0974

Gnomad4 EAS exome AF: 0.0884

Gnomad4 SAS exome AF: 0.0584

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0829

Gnomad4 OTH exome AF: 0.0921

GnomAD4 genome AF: 0.101 AC: 15425 AN: 152142 Hom.: 834 Cov.: 31 AF XY: 0.102 AC XY: 7608 AN XY: 74388

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0890

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0577

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.0850

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0849 Hom.: 557

Bravo AF: 0.102

Asia WGS AF: 0.0870 AC: 302 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.95
CADD	Benign	1.5
DANN	Benign	0.51

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: rs11076174; hg19: chr16-57003146; COSMIC: COSV52364539;