16-56972678-C-T

Variant names:

• chr16-56972678-C-T
• rs7499892
• NM_000078.3:c.750+595C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000078.3(CETP):​c.750+595C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,138 control chromosomes in the GnomAD database, including 4,956 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4956 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409
• Publications: 97 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.750+595C>T		intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.750+595C>T		intron	N/A	NP_001273014.1	A0A0S2Z3I8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	ENST00000200676.8	TSL:1 MANE Select	c.750+595C>T		intron	N/A	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.750+595C>T		intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.750+595C>T		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36068 AN: 152020 Hom.: 4939 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.237 AC: 36125 AN: 152138 Hom.: 4956 Cov.: 33 AF XY: 0.237 AC XY: 17624 AN XY: 74366

African (AFR) AF: 0.377 AC: 15634 AN: 41478

American (AMR) AF: 0.227 AC: 3476 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 545 AN: 3472

East Asian (EAS) AF: 0.166 AC: 858 AN: 5174

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4822

European-Finnish (FIN) AF: 0.164 AC: 1733 AN: 10590

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12250 AN: 67984

Other (OTH) AF: 0.221 AC: 467 AN: 2114

Alfa AF: 0.191 Hom.: 10006

Bravo AF: 0.247

Asia WGS AF: 0.193 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.63
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs7499892; hg19: chr16-57006590;