chr16-56973280-T-C

Position:

• chr16-56973280-T-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.751-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 1,595,658 control chromosomes in the GnomAD database, including 3,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (461 hom., cov: 32)
  • Exomes 𝑓: 0.063 (3126 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.605

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 16-56973280-T-C is Benign according to our data. Variant chr16-56973280-T-C is described in ClinVar as [Benign]. Clinvar id is 1297243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56973280-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.751-51T>C		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.750+1197T>C		intron_variant			NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.751-51T>C		intron_variant		1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.750+1197T>C		intron_variant		1		ENSP00000369106.2
CETP	ENST00000566128.1	c.556-51T>C		intron_variant		5		ENSP00000456276.1
CETP	ENST00000569082.1	n.853-51T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10889 AN: 152162 Hom.: 459 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.0665

GnomAD3 exomes AF: 0.0594 AC: 14705 AN: 247614 Hom.: 533 AF XY: 0.0596 AC XY: 7995 AN XY: 134196

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.0337

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.000491

Gnomad SAS exome AF: 0.0576

Gnomad FIN exome AF: 0.0436

Gnomad NFE exome AF: 0.0662

Gnomad OTH exome AF: 0.0724

GnomAD4 exome AF: 0.0627 AC: 90556 AN: 1443378 Hom.: 3126 Cov.: 29 AF XY: 0.0627 AC XY: 45035 AN XY: 718822

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0351

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.000354

Gnomad4 SAS exome AF: 0.0593

Gnomad4 FIN exome AF: 0.0479

Gnomad4 NFE exome AF: 0.0639

Gnomad4 OTH exome AF: 0.0629

GnomAD4 genome AF: 0.0716 AC: 10900 AN: 152280 Hom.: 461 Cov.: 32 AF XY: 0.0677 AC XY: 5037 AN XY: 74456

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0609

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0628

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0686 Hom.: 742

Bravo AF: 0.0743

Asia WGS AF: 0.0360 AC: 125 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	This variant is associated with the following publications: (PMID: 24393849, 22403620) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.90

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: rs9930761; hg19: chr16-57007192;