16-56962299-G-A

Position:

• chr16-56962299-G-A

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+202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 737,362 control chromosomes in the GnomAD database, including 65,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11865 hom., cov: 31)
  • Exomes 𝑓: 0.42 (53322 hom.)
• Consequence: CETP NM_000078.3 intron
• Scores: Splicing: ADA: 0.0001408
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01

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=-0.82).
• BP6: Variant 16-56962299-G-A is Benign according to our data. Variant chr16-56962299-G-A is described in ClinVar as [Benign]. Clinvar id is 1255212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56962299-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CETP	NM_000078.3	c.118+202G>A		intron_variant		ENST00000200676.8
CETP	NM_001286085.2	c.118+202G>A		intron_variant
CETP	XM_006721124.4	c.118+202G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8	c.118+202G>A		intron_variant		1	NM_000078.3	P1
CETP	ENST00000379780.6	c.118+202G>A		intron_variant		1
CETP	ENST00000566128.1	c.-78+3G>A		splice_donor_region_variant, intron_variant		5
CETP	ENST00000569082.1	n.116+202G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58532 AN: 151832 Hom.: 11855 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.424 AC: 248464 AN: 585410 Hom.: 53322 Cov.: 3 AF XY: 0.428 AC XY: 136870 AN XY: 319762

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.390

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.412

GnomAD4 genome AF: 0.386 AC: 58585 AN: 151952 Hom.: 11865 Cov.: 31 AF XY: 0.391 AC XY: 29016 AN XY: 74246

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.381

Alfa AF: 0.380 Hom.: 1676

Bravo AF: 0.376

Asia WGS AF: 0.410 AC: 1428 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	-0.82
CADD	Benign	12
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.51		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.51		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs711752; hg19: chr16-56996211; COSMIC: COSV52362751;