16-56962246-T-C

Position:

• chr16-56962246-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.118+149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 768,876 control chromosomes in the GnomAD database, including 102,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20861 hom., cov: 31)
  • Exomes 𝑓: 0.51 (81252 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.13

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=-0.97).
• BP6: Variant 16-56962246-T-C is Benign according to our data. Variant chr16-56962246-T-C is described in ClinVar as [Benign]. Clinvar id is 1267499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56962246-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.118+149T>C		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.118+149T>C		intron_variant			NP_001273014.1
CETP	XM_006721124.4	c.118+149T>C		intron_variant			XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.118+149T>C		intron_variant		1	NM_000078.3	ENSP00000200676	P1
CETP	ENST00000379780.6	c.118+149T>C		intron_variant		1		ENSP00000369106
CETP	ENST00000566128.1	c.-128T>C		5_prime_UTR_variant	1/16	5		ENSP00000456276
CETP	ENST00000569082.1	n.116+149T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79155 AN: 151654 Hom.: 20829 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.510 AC: 315024 AN: 617104 Hom.: 81252 Cov.: 7 AF XY: 0.515 AC XY: 173009 AN XY: 335656

Gnomad4 AFR exome AF: 0.566

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.523

Gnomad4 SAS exome AF: 0.608

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.522 AC: 79231 AN: 151772 Hom.: 20861 Cov.: 31 AF XY: 0.526 AC XY: 38979 AN XY: 74154

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.501

Alfa AF: 0.512 Hom.: 12485

Bravo AF: 0.522

Asia WGS AF: 0.542 AC: 1887 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	-0.97
CADD	Benign	0.37
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3816117; hg19: chr16-56996158;