rs7205804

Positions:

• chr16-56970977-G-A
• chr16-56970977-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000078.3(CETP):​c.528-56G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,533,662 control chromosomes in the GnomAD database, including 138,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (10415 hom., cov: 32)
  • Exomes 𝑓: 0.43 (127982 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-56970977-G-A is Benign according to our data. Variant chr16-56970977-G-A is described in ClinVar as [Benign]. Clinvar id is 1249684.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56970977-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CETP	NM_000078.3	c.528-56G>A		intron_variant		ENST00000200676.8
CETP	NM_001286085.2	c.528-56G>A		intron_variant
CETP	XM_006721124.4	c.528-56G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CETP	ENST00000200676.8	c.528-56G>A		intron_variant		1	NM_000078.3	P1
CETP	ENST00000379780.6	c.528-56G>A		intron_variant		1
CETP	ENST00000566128.1	c.333-56G>A		intron_variant		5
CETP	ENST00000569082.1	n.526-56G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52623 AN: 151932 Hom.: 10421 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.427 AC: 589587 AN: 1381612 Hom.: 127982 AF XY: 0.430 AC XY: 297635 AN XY: 691882

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.410

GnomAD4 genome AF: 0.346 AC: 52614 AN: 152050 Hom.: 10415 Cov.: 32 AF XY: 0.348 AC XY: 25897 AN XY: 74318

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.341

Alfa AF: 0.405 Hom.: 14551

Bravo AF: 0.328

Asia WGS AF: 0.368 AC: 1281 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.86
CADD	Benign	0.29
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7205804; hg19: chr16-57004889; COSMIC: COSV52362249;