rs4784744

Variant names:

• chr16-56977273-G-A
• rs4784744
• NM_000078.3:c.982-818G>A

Variant summary

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

The NM_000078.3(CETP):​c.982-818G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,922 control chromosomes in the GnomAD database, including 7,683 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 (7683 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809
• Publications: 30 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 (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.982-818G>A		intron_variant	Intron 10 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.802-818G>A		intron_variant	Intron 9 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.982-818G>A		intron_variant	Intron 10 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.802-818G>A		intron_variant	Intron 9 of 14	1		ENSP00000369106.2
CETP	ENST00000650358.1	n.562G>A		non_coding_transcript_exon_variant	Exon 1 of 5
CETP	ENST00000566128.1	c.787-818G>A		intron_variant	Intron 10 of 15	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45616 AN: 151804 Hom.: 7674 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.300 AC: 45637 AN: 151922 Hom.: 7683 Cov.: 32 AF XY: 0.302 AC XY: 22445 AN XY: 74230

African (AFR) AF: 0.158 AC: 6528 AN: 41444

American (AMR) AF: 0.379 AC: 5781 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1078 AN: 3472

East Asian (EAS) AF: 0.566 AC: 2919 AN: 5158

South Asian (SAS) AF: 0.266 AC: 1278 AN: 4812

European-Finnish (FIN) AF: 0.358 AC: 3770 AN: 10534

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23227 AN: 67924

Other (OTH) AF: 0.336 AC: 709 AN: 2110

Alfa AF: 0.337 Hom.: 19873

Bravo AF: 0.300

Asia WGS AF: 0.392 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.65
PhyloP100		0.81
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: rs4784744; hg19: chr16-57011185;