rs11076175

Variant names:

• chr16-56972466-A-G
• rs11076175
• NM_000078.3:c.750+383A>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.750+383A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,224 control chromosomes in the GnomAD database, including 3,147 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 0.20 (3147 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553
• Publications: 39 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 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.750+383A>G		intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.750+383A>G		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.750+383A>G		intron	N/A	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.750+383A>G		intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.750+383A>G		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30011 AN: 152106 Hom.: 3142 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.197 AC: 30036 AN: 152224 Hom.: 3147 Cov.: 33 AF XY: 0.197 AC XY: 14636 AN XY: 74438

African (AFR) AF: 0.248 AC: 10290 AN: 41524

American (AMR) AF: 0.214 AC: 3273 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3470

East Asian (EAS) AF: 0.110 AC: 570 AN: 5178

South Asian (SAS) AF: 0.190 AC: 916 AN: 4828

European-Finnish (FIN) AF: 0.164 AC: 1740 AN: 10604

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12216 AN: 68010

Other (OTH) AF: 0.199 AC: 420 AN: 2108

Alfa AF: 0.210 Hom.: 1075

Bravo AF: 0.202

Asia WGS AF: 0.153 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.33
PhyloP100		-0.55
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: rs11076175; hg19: chr16-57006378;