16-56973698-G-A

Position:

• chr16-56973698-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.930+188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,064 control chromosomes in the GnomAD database, including 18,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.49 (18642 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.880

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=-0.71).
• BP6: Variant 16-56973698-G-A is Benign according to our data. Variant chr16-56973698-G-A is described in ClinVar as [Benign]. Clinvar id is 1271769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56973698-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.930+188G>A		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.751-1403G>A		intron_variant			NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.930+188G>A		intron_variant		1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.751-1403G>A		intron_variant		1		ENSP00000369106.2
CETP	ENST00000566128.1	c.735+188G>A		intron_variant		5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74564 AN: 151944 Hom.: 18633 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.528

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.491 AC: 74599 AN: 152064 Hom.: 18642 Cov.: 33 AF XY: 0.488 AC XY: 36299 AN XY: 74336

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.531

Alfa AF: 0.506 Hom.: 2420

Bravo AF: 0.479

Asia WGS AF: 0.490 AC: 1704 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	-0.71
CADD	Benign	11
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs158477; hg19: chr16-57007610;