rs12720889

Variant names:

• chr16-56978651-A-T
• rs12720889
• NM_000078.3:c.1146+396A>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.1146+396A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 146,014 control chromosomes in the GnomAD database, including 5,675 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 0.27 (5675 hom., cov: 29)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 10 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 (SAS) allele frequency at 95% confidence interval = 0.365 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.1146+396A>T		intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.966+396A>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.1146+396A>T		intron	N/A	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.966+396A>T		intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.1254+396A>T		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 39796 AN: 145926 Hom.: 5676 Cov.: 29

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.273 AC: 39804 AN: 146014 Hom.: 5675 Cov.: 29 AF XY: 0.275 AC XY: 19513 AN XY: 70892

African (AFR) AF: 0.195 AC: 7889 AN: 40530

American (AMR) AF: 0.233 AC: 3124 AN: 13396

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1353 AN: 3434

East Asian (EAS) AF: 0.240 AC: 977 AN: 4066

South Asian (SAS) AF: 0.380 AC: 1703 AN: 4480

European-Finnish (FIN) AF: 0.357 AC: 3537 AN: 9912

Middle Eastern (MID) AF: 0.390 AC: 113 AN: 290

European-Non Finnish (NFE) AF: 0.301 AC: 20160 AN: 66990

Other (OTH) AF: 0.287 AC: 577 AN: 2010

Alfa AF: 0.270 Hom.: 521

Bravo AF: 0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.65
PhyloP100		-0.56
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: rs12720889; hg19: chr16-57012563;