NM_000078.3:c.930+312A>C

Variant names:

• chr16-56973822-A-C
• rs158478
• NM_000078.3:c.930+312A>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.930+312A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,054 control chromosomes in the GnomAD database, including 17,023 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 0.46 (17023 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.930+312A>C		intron_variant	Intron 9 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.751-1279A>C		intron_variant	Intron 8 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.930+312A>C		intron_variant	Intron 9 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.751-1279A>C		intron_variant	Intron 8 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.735+312A>C		intron_variant	Intron 9 of 15	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70398 AN: 151936 Hom.: 17013 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.463 AC: 70427 AN: 152054 Hom.: 17023 Cov.: 33 AF XY: 0.462 AC XY: 34306 AN XY: 74330

African (AFR) AF: 0.337 AC: 13983 AN: 41464

American (AMR) AF: 0.432 AC: 6600 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2094 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2779 AN: 5166

South Asian (SAS) AF: 0.417 AC: 2010 AN: 4822

European-Finnish (FIN) AF: 0.559 AC: 5895 AN: 10546

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35391 AN: 67982

Other (OTH) AF: 0.513 AC: 1084 AN: 2112

Alfa AF: 0.348 Hom.: 935

Bravo AF: 0.450

Asia WGS AF: 0.486 AC: 1689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.1
DANN	Benign	0.27
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs158478; hg19: chr16-57007734;