rs708272

Positions:

• chr16-56962376-G-A
• chr16-56962376-G-C

Variant summary

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

The NM_000078.3(CETP):​c.118+279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 665,408 control chromosomes in the GnomAD database, including 58,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11832 hom., cov: 30)
  • Exomes 𝑓: 0.42 (46916 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.65

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=-0.98).
• BP6: Variant 16-56962376-G-A is Benign according to our data. Variant chr16-56962376-G-A is described in ClinVar as [Benign]. Clinvar id is 1239762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56962376-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.118+279G>A		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.118+279G>A		intron_variant			NP_001273014.1
CETP	XM_006721124.4	c.118+279G>A		intron_variant			XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.118+279G>A		intron_variant		1	NM_000078.3	ENSP00000200676	P1
CETP	ENST00000379780.6	c.118+279G>A		intron_variant		1		ENSP00000369106
CETP	ENST00000566128.1	c.-78+80G>A		intron_variant		5		ENSP00000456276
CETP	ENST00000569082.1	n.116+279G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58415 AN: 151616 Hom.: 11821 Cov.: 30

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.384

GnomAD3 exomes AF: 0.424 AC: 96025 AN: 226300 Hom.: 20571 AF XY: 0.428 AC XY: 53503 AN XY: 124984

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.476

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.392

Gnomad SAS exome AF: 0.465

Gnomad FIN exome AF: 0.437

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.426

GnomAD4 exome AF: 0.423 AC: 217317 AN: 513672 Hom.: 46916 Cov.: 0 AF XY: 0.427 AC XY: 121515 AN XY: 284554

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.439

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.410

GnomAD4 genome AF: 0.385 AC: 58469 AN: 151736 Hom.: 11832 Cov.: 30 AF XY: 0.390 AC XY: 28940 AN XY: 74114

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.382

Alfa AF: 0.426 Hom.: 15714

Bravo AF: 0.376

Asia WGS AF: 0.407 AC: 1417 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Coronary artery disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Rasad Genetic Department, Rasad Pathobiology and Genetic Laboratory

May 12, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.049
DANN	Benign	0.39

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: rs708272; hg19: chr16-56996288; COSMIC: COSV52361236;