16-56968820-T-G

Variant names:

• chr16-56968820-T-G
• rs9939224
• NM_000078.3:c.234-566T>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.234-566T>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 150,930 control chromosomes in the GnomAD database, including 43,149 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 (43149 hom., cov: 27)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 57 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.234-566T>G		intron_variant	Intron 2 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.234-566T>G		intron_variant	Intron 2 of 14		NP_001273014.1
CETP	XM_006721124.4	c.234-566T>G		intron_variant	Intron 2 of 8		XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.234-566T>G		intron_variant	Intron 2 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.234-566T>G		intron_variant	Intron 2 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.39-566T>G		intron_variant	Intron 2 of 15	5		ENSP00000456276.1
CETP	ENST00000569082.1	n.232-566T>G		intron_variant	Intron 2 of 8	5

Frequencies

GnomAD3 genomes AF: 0.753 AC: 113564 AN: 150814 Hom.: 43124 Cov.: 27

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.753 AC: 113636 AN: 150930 Hom.: 43149 Cov.: 27 AF XY: 0.754 AC XY: 55490 AN XY: 73628

African (AFR) AF: 0.657 AC: 26942 AN: 41010

American (AMR) AF: 0.752 AC: 11408 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2846 AN: 3452

East Asian (EAS) AF: 0.869 AC: 4451 AN: 5124

South Asian (SAS) AF: 0.789 AC: 3749 AN: 4754

European-Finnish (FIN) AF: 0.780 AC: 8061 AN: 10334

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53546 AN: 67780

Other (OTH) AF: 0.758 AC: 1592 AN: 2100

Alfa AF: 0.784 Hom.: 192062

Bravo AF: 0.748

Asia WGS AF: 0.817 AC: 2840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.25
PhyloP100		-0.51
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: rs9939224; hg19: chr16-57002732;