rs2033254

Variant names:

• chr16-56976073-T-C
• rs2033254
• NM_000078.3:c.981+922T>C

Variant summary

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

The ENST00000200676.8(CETP):​c.981+922T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,090 control chromosomes in the GnomAD database, including 8,973 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 0.34 (8973 hom., cov: 32)
• Consequence: CETP ENST00000200676.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000200676.8. 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.981+922T>C		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.801+922T>C		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.981+922T>C		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.801+922T>C		intron	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.786+922T>C		intron	N/A	ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51294 AN: 151972 Hom.: 8960 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.338 AC: 51344 AN: 152090 Hom.: 8973 Cov.: 32 AF XY: 0.335 AC XY: 24888 AN XY: 74330

African (AFR) AF: 0.372 AC: 15424 AN: 41490

American (AMR) AF: 0.330 AC: 5048 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 973 AN: 3470

East Asian (EAS) AF: 0.120 AC: 619 AN: 5168

South Asian (SAS) AF: 0.312 AC: 1502 AN: 4812

European-Finnish (FIN) AF: 0.297 AC: 3136 AN: 10568

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23663 AN: 67970

Other (OTH) AF: 0.316 AC: 667 AN: 2110

Alfa AF: 0.346 Hom.: 4497

Bravo AF: 0.338

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.50
PhyloP100		0.16
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: rs2033254; hg19: chr16-57009985;