NM_000078.3:c.1264G>C

Variant names:

• chr16-56982180-G-C
• rs5882
• NM_000078.3:c.1264G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000078.3(CETP):​c.1264G>C​(p.Val422Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V422I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CETP NM_000078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 336 publications found

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]

CETP Gene-Disease associations (from GenCC):

• cholesterol-ester transfer protein deficiency

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049870342).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.1264G>C	p.Val422Leu	missense	Exon 14 of 16	NP_000069.2
	CETP	NM_001286085.2		c.1084G>C	p.Val362Leu	missense	Exon 13 of 15	NP_001273014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	ENST00000200676.8	TSL:1 MANE Select	c.1264G>C	p.Val422Leu	missense	Exon 14 of 16	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.1084G>C	p.Val362Leu	missense	Exon 13 of 15	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.1069G>C	p.Val357Leu	missense	Exon 14 of 16	ENSP00000456276.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 152656

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0010
DANN	Benign	0.33
DEOGEN2	Benign	0.070	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.69	N
PhyloP100		-2.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.83	N
REVEL	Benign	0.0050
Sift	Benign	0.63	T
Sift4G	Benign	0.58	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.35		Gain of disorder (P = 0.1909)
MVP		0.067
MPC		0.13
ClinPred		0.034	T
GERP RS		-6.7
Varity_R		0.028
gMVP		0.17

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

Other links and lift over

dbSNP: rs5882; hg19: chr16-57016092;