rs12708980

Positions:

• chr16-56978467-T-G

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.1146+212T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,832 control chromosomes in the GnomAD database, including 9,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (9657 hom., cov: 31)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.449

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=-0.84).
• BP6: Variant 16-56978467-T-G is Benign according to our data. Variant chr16-56978467-T-G is described in ClinVar as [Benign]. Clinvar id is 1278306.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56978467-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.1146+212T>G		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.966+212T>G		intron_variant			NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.1146+212T>G		intron_variant		1	NM_000078.3	ENSP00000200676	P1
CETP	ENST00000379780.6	c.966+212T>G		intron_variant		1		ENSP00000369106
CETP	ENST00000566128.1	c.951+212T>G		intron_variant		5		ENSP00000456276
CETP	ENST00000650358.1	n.1544+212T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53297 AN: 151716 Hom.: 9642 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.351 AC: 53339 AN: 151832 Hom.: 9657 Cov.: 31 AF XY: 0.348 AC XY: 25835 AN XY: 74220

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.332

Alfa AF: 0.358 Hom.: 17243

Bravo AF: 0.354

Asia WGS AF: 0.232 AC: 806 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

Sep 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.68

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: rs12708980; hg19: chr16-57012379;