chr16-56962376-G-A

Variant names:

• chr16-56962376-G-A
• rs708272
• NM_000078.3:c.118+279G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 240 publications found

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 Gene-Disease associations (from GenCC):

• cholesterol-ester transfer protein deficiency

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1239762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.118+279G>A		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.118+279G>A		intron	N/A	NP_001273014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	ENST00000200676.8	TSL:1 MANE Select	c.118+279G>A		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.118+279G>A		intron	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.-78+80G>A		intron	N/A	ENSP00000456276.1

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

GnomAD2 exomes AF: 0.424 AC: 96025 AN: 226300 AF XY: 0.428

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 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

African (AFR) AF: 0.253 AC: 3873 AN: 15284

American (AMR) AF: 0.469 AC: 18797 AN: 40108

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 6507 AN: 17466

East Asian (EAS) AF: 0.380 AC: 10185 AN: 26820

South Asian (SAS) AF: 0.471 AC: 31899 AN: 67752

European-Finnish (FIN) AF: 0.439 AC: 13013 AN: 29622

Middle Eastern (MID) AF: 0.391 AC: 1414 AN: 3618

European-Non Finnish (NFE) AF: 0.421 AC: 120766 AN: 286530

Other (OTH) AF: 0.410 AC: 10863 AN: 26472

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

African (AFR) AF: 0.265 AC: 10960 AN: 41402

American (AMR) AF: 0.420 AC: 6399 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1333 AN: 3472

East Asian (EAS) AF: 0.375 AC: 1926 AN: 5132

South Asian (SAS) AF: 0.462 AC: 2214 AN: 4794

European-Finnish (FIN) AF: 0.452 AC: 4752 AN: 10502

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29492 AN: 67878

Other (OTH) AF: 0.382 AC: 803 AN: 2104

Alfa AF: 0.414 Hom.: 37209

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Coronary artery disorder Benign:1

May 12, 2022

Rasad Genetic Department, Rasad Pathobiology and Genetic Laboratory

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.049
DANN	Benign	0.39
PhyloP100		-1.7
PromoterAI		-0.0070	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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