chr16-56965346-A-C

Variant names:

• chr16-56965346-A-C
• rs7203984
• NM_000078.3:c.233+2222A>C

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+2222A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,126 control chromosomes in the GnomAD database, including 8,866 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 0.30 (8866 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527
• Publications: 35 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 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+2222A>C		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.233+2222A>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.233+2222A>C		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.233+2222A>C		intron	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.38+2222A>C		intron	N/A	ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46289 AN: 152008 Hom.: 8831 Cov.: 33

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.305 AC: 46390 AN: 152126 Hom.: 8866 Cov.: 33 AF XY: 0.304 AC XY: 22637 AN XY: 74382

African (AFR) AF: 0.539 AC: 22328 AN: 41448

American (AMR) AF: 0.327 AC: 4995 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1305 AN: 5188

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4822

European-Finnish (FIN) AF: 0.192 AC: 2036 AN: 10602

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13264 AN: 67994

Other (OTH) AF: 0.291 AC: 616 AN: 2114

Alfa AF: 0.235 Hom.: 11068

Bravo AF: 0.324

Asia WGS AF: 0.275 AC: 954 AN: 3476

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	0.43
PhyloP100		-0.53
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: rs7203984; hg19: chr16-56999258; COSMIC: COSV52364641;