rs5883

Variant names:

• chr16-56973441-C-T
• rs5883
• NM_000078.3:c.861C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000078.3(CETP):​c.861C>T​(p.Phe287Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,614,184 control chromosomes in the GnomAD database, including 2,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (399 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2288 hom.)
• Consequence: CETP NM_000078.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.649
• Publications: 68 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-56973441-C-T is Benign according to our data. Variant chr16-56973441-C-T is described in ClinVar as Benign. ClinVar VariationId is 319984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.649 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.861C>T	p.Phe287Phe	synonymous	Exon 9 of 16	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.750+1358C>T		intron	N/A	NP_001273014.1	A0A0S2Z3I8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	ENST00000200676.8	TSL:1 MANE Select	c.861C>T	p.Phe287Phe	synonymous	Exon 9 of 16	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.750+1358C>T		intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.861C>T	p.Phe287Phe	synonymous	Exon 9 of 17	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.0648 AC: 9861 AN: 152190 Hom.: 399 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0574

GnomAD2 exomes AF: 0.0513 AC: 12897 AN: 251464 AF XY: 0.0500

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0294

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.000489

Gnomad FIN exome AF: 0.0396

Gnomad NFE exome AF: 0.0568

Gnomad OTH exome AF: 0.0638

GnomAD4 exome AF: 0.0525 AC: 76707 AN: 1461876 Hom.: 2288 Cov.: 33 AF XY: 0.0520 AC XY: 37795 AN XY: 727244

African (AFR) AF: 0.111 AC: 3720 AN: 33480

American (AMR) AF: 0.0308 AC: 1378 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 3233 AN: 26136

East Asian (EAS) AF: 0.000453 AC: 18 AN: 39698

South Asian (SAS) AF: 0.0380 AC: 3276 AN: 86258

European-Finnish (FIN) AF: 0.0441 AC: 2356 AN: 53410

Middle Eastern (MID) AF: 0.0650 AC: 375 AN: 5768

European-Non Finnish (NFE) AF: 0.0532 AC: 59115 AN: 1112006

Other (OTH) AF: 0.0536 AC: 3236 AN: 60396

GnomAD4 genome AF: 0.0648 AC: 9864 AN: 152308 Hom.: 399 Cov.: 32 AF XY: 0.0611 AC XY: 4554 AN XY: 74486

African (AFR) AF: 0.106 AC: 4408 AN: 41550

American (AMR) AF: 0.0402 AC: 616 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5190

South Asian (SAS) AF: 0.0375 AC: 181 AN: 4830

European-Finnish (FIN) AF: 0.0354 AC: 376 AN: 10618

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0533 AC: 3625 AN: 68022

Other (OTH) AF: 0.0587 AC: 124 AN: 2114

Alfa AF: 0.0601 Hom.: 1296

Bravo AF: 0.0680

Asia WGS AF: 0.0260 AC: 89 AN: 3478

EpiCase AF: 0.0545

EpiControl AF: 0.0593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hyperalphalipoproteinemia 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.76
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs5883; hg19: chr16-57007353; COSMIC: COSV52362633; COSMIC: COSV52362633;