rs891144

Positions:

• chr16-56978024-C-T

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.982-67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 1,578,790 control chromosomes in the GnomAD database, including 2,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (882 hom., cov: 32)
  • Exomes 𝑓: 0.024 (1462 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.12

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 16-56978024-C-T is Benign according to our data. Variant chr16-56978024-C-T is described in ClinVar as [Benign]. Clinvar id is 1228339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.982-67C>T		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.802-67C>T		intron_variant			NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.982-67C>T		intron_variant		1	NM_000078.3	ENSP00000200676	P1
CETP	ENST00000379780.6	c.802-67C>T		intron_variant		1		ENSP00000369106
CETP	ENST00000566128.1	c.787-67C>T		intron_variant		5		ENSP00000456276
CETP	ENST00000650358.1	n.1313C>T		non_coding_transcript_exon_variant	1/5

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10936 AN: 152102 Hom.: 879 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0932

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0608

GnomAD4 exome AF: 0.0237 AC: 33771 AN: 1426570 Hom.: 1462 AF XY: 0.0236 AC XY: 16680 AN XY: 707036

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.00624

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.0495

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.00991

Gnomad4 OTH exome AF: 0.0326

GnomAD4 genome AF: 0.0721 AC: 10969 AN: 152220 Hom.: 882 Cov.: 32 AF XY: 0.0721 AC XY: 5370 AN XY: 74442

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.0937

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0532

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0290 Hom.: 175

Bravo AF: 0.0851

Asia WGS AF: 0.0980 AC: 340 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	Apr 08, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.064
DANN	Benign	0.59

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: rs891144; hg19: chr16-57011936; COSMIC: COSV52363520; COSMIC: COSV52363520;