NM_000078.3:c.930+626G>A

Variant names:

• chr16-56974136-G-A
• rs158479
• NM_000078.3:c.930+626G>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.930+626G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,842 control chromosomes in the GnomAD database, including 17,278 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 0.47 (17278 hom., cov: 31)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 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.930+626G>A		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.751-965G>A		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.930+626G>A		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.751-965G>A		intron	N/A	ENSP00000369106.2
	CETP	ENST00000858282.1		c.930+626G>A		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70802 AN: 151724 Hom.: 17272 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.466 AC: 70828 AN: 151842 Hom.: 17278 Cov.: 31 AF XY: 0.465 AC XY: 34505 AN XY: 74212

African (AFR) AF: 0.333 AC: 13786 AN: 41386

American (AMR) AF: 0.432 AC: 6599 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2089 AN: 3466

East Asian (EAS) AF: 0.539 AC: 2785 AN: 5170

South Asian (SAS) AF: 0.416 AC: 2005 AN: 4814

European-Finnish (FIN) AF: 0.559 AC: 5876 AN: 10512

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35961 AN: 67932

Other (OTH) AF: 0.505 AC: 1061 AN: 2102

Alfa AF: 0.489 Hom.: 2293

Bravo AF: 0.453

Asia WGS AF: 0.486 AC: 1689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.82
PhyloP100		-1.2
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: rs158479; hg19: chr16-57008048;