NM_000078.3:c.233+2292C>T

Variant names:

• chr16-56965416-C-T
• rs11508026
• NM_000078.3:c.233+2292C>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.233+2292C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,346 control chromosomes in the GnomAD database, including 9,685 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 0.33 (9685 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 39 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.437 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.233+2292C>T		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.233+2292C>T		intron	N/A	NP_001273014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	ENST00000200676.8	TSL:1 MANE Select	c.233+2292C>T		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.233+2292C>T		intron	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.38+2292C>T		intron	N/A	ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49212 AN: 151228 Hom.: 9690 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.325 AC: 49203 AN: 151346 Hom.: 9685 Cov.: 32 AF XY: 0.328 AC XY: 24243 AN XY: 73924

African (AFR) AF: 0.0966 AC: 3972 AN: 41110

American (AMR) AF: 0.332 AC: 5054 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1344 AN: 3442

East Asian (EAS) AF: 0.286 AC: 1469 AN: 5134

South Asian (SAS) AF: 0.453 AC: 2168 AN: 4784

European-Finnish (FIN) AF: 0.423 AC: 4446 AN: 10510

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29467 AN: 67834

Other (OTH) AF: 0.329 AC: 694 AN: 2108

Alfa AF: 0.291 Hom.: 2749

Bravo AF: 0.304

Asia WGS AF: 0.343 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.44
DANN	Benign	0.50
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: rs11508026; hg19: chr16-56999328;