chr16-56974596-A-T

Variant names:

• chr16-56974596-A-T
• rs289715
• NM_000078.3:c.931-505A>T

Variant summary

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

The NM_000078.3(CETP):​c.931-505A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,250 control chromosomes in the GnomAD database, including 55,492 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 0.85 (55492 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.877
• Publications: 18 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.878 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.931-505A>T		intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.751-505A>T		intron	N/A	NP_001273014.1	A0A0S2Z3I8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	ENST00000200676.8	TSL:1 MANE Select	c.931-505A>T		intron	N/A	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.751-505A>T		intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.931-505A>T		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129695 AN: 152132 Hom.: 55447 Cov.: 33

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.853 AC: 129796 AN: 152250 Hom.: 55492 Cov.: 33 AF XY: 0.848 AC XY: 63165 AN XY: 74456

African (AFR) AF: 0.814 AC: 33793 AN: 41524

American (AMR) AF: 0.847 AC: 12967 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3075 AN: 3470

East Asian (EAS) AF: 0.793 AC: 4109 AN: 5184

South Asian (SAS) AF: 0.759 AC: 3659 AN: 4820

European-Finnish (FIN) AF: 0.872 AC: 9256 AN: 10616

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.884 AC: 60095 AN: 68016

Other (OTH) AF: 0.877 AC: 1855 AN: 2116

Alfa AF: 0.868 Hom.: 27564

Bravo AF: 0.850

Asia WGS AF: 0.791 AC: 2749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.16
PhyloP100		-0.88
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: rs289715; hg19: chr16-57008508;