chr16-56977331-C-T

Variant names:

• chr16-56977331-C-T
• rs12720898
• NM_000078.3:c.982-760C>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.982-760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 152,180 control chromosomes in the GnomAD database, including 366 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 0.058 (366 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 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.982-760C>T		intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.802-760C>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.982-760C>T		intron	N/A	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.802-760C>T		intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.1089+727C>T		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8868 AN: 152062 Hom.: 364 Cov.: 32

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0430

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0735

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0583 AC: 8874 AN: 152180 Hom.: 366 Cov.: 32 AF XY: 0.0593 AC XY: 4410 AN XY: 74410

African (AFR) AF: 0.0173 AC: 718 AN: 41516

American (AMR) AF: 0.0430 AC: 657 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3472

East Asian (EAS) AF: 0.102 AC: 529 AN: 5178

South Asian (SAS) AF: 0.110 AC: 531 AN: 4818

European-Finnish (FIN) AF: 0.0812 AC: 861 AN: 10598

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0736 AC: 5003 AN: 67992

Other (OTH) AF: 0.0735 AC: 155 AN: 2110

Alfa AF: 0.0686 Hom.: 651

Bravo AF: 0.0525

Asia WGS AF: 0.117 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.87
PhyloP100		-1.4
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: rs12720898; hg19: chr16-57011243;