16-56966037-A-G

Variant names:

• chr16-56966037-A-G
• rs708273
• NM_000078.3:c.233+2913A>G

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+2913A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,090 control chromosomes in the GnomAD database, including 43,652 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 0.75 (43652 hom., cov: 31)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 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+2913A>G		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.233+2913A>G		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+2913A>G		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.233+2913A>G		intron	N/A	ENSP00000369106.2
	CETP	ENST00000858282.1		c.233+2913A>G		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114381 AN: 151970 Hom.: 43598 Cov.: 31

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.753 AC: 114495 AN: 152090 Hom.: 43652 Cov.: 31 AF XY: 0.753 AC XY: 55996 AN XY: 74340

African (AFR) AF: 0.871 AC: 36105 AN: 41474

American (AMR) AF: 0.739 AC: 11286 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2394 AN: 3470

East Asian (EAS) AF: 0.624 AC: 3223 AN: 5166

South Asian (SAS) AF: 0.793 AC: 3815 AN: 4812

European-Finnish (FIN) AF: 0.698 AC: 7377 AN: 10572

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47911 AN: 67998

Other (OTH) AF: 0.725 AC: 1532 AN: 2114

Alfa AF: 0.716 Hom.: 24945

Bravo AF: 0.758

Asia WGS AF: 0.711 AC: 2473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.59
DANN	Benign	0.41
PhyloP100		-0.82
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: rs708273; hg19: chr16-56999949;