16-56962192-C-A

Position:

• chr16-56962192-C-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+95C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,043,986 control chromosomes in the GnomAD database, including 2,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (472 hom., cov: 32)
  • Exomes 𝑓: 0.053 (1593 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.353

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=-0.9).
• BP6: Variant 16-56962192-C-A is Benign according to our data. Variant chr16-56962192-C-A is described in ClinVar as [Benign]. Clinvar id is 1282916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.118+95C>A		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.118+95C>A		intron_variant			NP_001273014.1
CETP	XM_006721124.4	c.118+95C>A		intron_variant			XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.118+95C>A		intron_variant		1	NM_000078.3	ENSP00000200676	P1
CETP	ENST00000379780.6	c.118+95C>A		intron_variant		1		ENSP00000369106
CETP	ENST00000566128.1	c.-182C>A		5_prime_UTR_variant	1/16	5		ENSP00000456276
CETP	ENST00000569082.1	n.116+95C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10836 AN: 152126 Hom.: 471 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0586

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0718

GnomAD4 exome AF: 0.0529 AC: 47185 AN: 891742 Hom.: 1593 Cov.: 12 AF XY: 0.0540 AC XY: 25194 AN XY: 466458

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.0533

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.0618

Gnomad4 SAS exome AF: 0.0847

Gnomad4 FIN exome AF: 0.0492

Gnomad4 NFE exome AF: 0.0420

Gnomad4 OTH exome AF: 0.0628

GnomAD4 genome AF: 0.0712 AC: 10844 AN: 152244 Hom.: 472 Cov.: 32 AF XY: 0.0707 AC XY: 5261 AN XY: 74442

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0587

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0621

Gnomad4 SAS AF: 0.0845

Gnomad4 FIN AF: 0.0502

Gnomad4 NFE AF: 0.0427

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0485 Hom.: 192

Bravo AF: 0.0736

Asia WGS AF: 0.0780 AC: 273 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	Sep 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.74

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: rs17231534; hg19: chr16-56996104;