16-56962022-G-T

Position:

• chr16-56962022-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000078.3(CETP):​c.43G>T​(p.Ala15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A15G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CETP NM_000078.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0810

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057871073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.43G>T	p.Ala15Ser	missense_variant	1/16	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.43G>T	p.Ala15Ser	missense_variant	1/15		NP_001273014.1
CETP	XM_006721124.4	c.43G>T	p.Ala15Ser	missense_variant	1/9		XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.43G>T	p.Ala15Ser	missense_variant	1/16	1	NM_000078.3	ENSP00000200676	P1
CETP	ENST00000379780.6	c.43G>T	p.Ala15Ser	missense_variant	1/15	1		ENSP00000369106
CETP	ENST00000569082.1	n.41G>T		non_coding_transcript_exon_variant	1/9	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2022

The c.43G>T (p.A15S) alteration is located in exon 1 (coding exon 1) of the CETP gene. This alteration results from a G to T substitution at nucleotide position 43, causing the alanine (A) at amino acid position 15 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.6
DANN	Benign	0.89
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.46	N;N
REVEL	Benign	0.012
Sift	Benign	0.44	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0040	B;B
Vest4		0.036
MutPred		0.42		Gain of disorder (P = 0.0323);Gain of disorder (P = 0.0323);
MVP		0.34
MPC		0.12
ClinPred		0.11	T
GERP RS		-2.7
Varity_R		0.052
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-56995934;