16-56969234-T-C

Variant names:

• chr16-56969234-T-C
• rs11076174
• NM_000078.3:c.234-152T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000078.3(CETP):​c.234-152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 996,324 control chromosomes in the GnomAD database, including 4,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (834 hom., cov: 31)
  • Exomes 𝑓: 0.085 (3266 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0200
• Publications: 26 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 16-56969234-T-C is Benign according to our data. Variant chr16-56969234-T-C is described in ClinVar as Benign. ClinVar VariationId is 1182498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 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.234-152T>C		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.234-152T>C		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.234-152T>C		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.234-152T>C		intron	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.39-152T>C		intron	N/A	ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15404 AN: 152024 Hom.: 832 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0889

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0578

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0850

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0846 AC: 71435 AN: 844182 Hom.: 3266 AF XY: 0.0831 AC XY: 36861 AN XY: 443664

African (AFR) AF: 0.134 AC: 2891 AN: 21590

American (AMR) AF: 0.0850 AC: 3692 AN: 43426

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 2146 AN: 22042

East Asian (EAS) AF: 0.0884 AC: 3257 AN: 36858

South Asian (SAS) AF: 0.0584 AC: 4271 AN: 73160

European-Finnish (FIN) AF: 0.110 AC: 4537 AN: 41060

Middle Eastern (MID) AF: 0.0894 AC: 267 AN: 2988

European-Non Finnish (NFE) AF: 0.0829 AC: 46669 AN: 562848

Other (OTH) AF: 0.0921 AC: 3705 AN: 40210

GnomAD4 genome AF: 0.101 AC: 15425 AN: 152142 Hom.: 834 Cov.: 31 AF XY: 0.102 AC XY: 7608 AN XY: 74388

African (AFR) AF: 0.135 AC: 5595 AN: 41490

American (AMR) AF: 0.0890 AC: 1361 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3470

East Asian (EAS) AF: 0.102 AC: 528 AN: 5164

South Asian (SAS) AF: 0.0577 AC: 278 AN: 4822

European-Finnish (FIN) AF: 0.120 AC: 1275 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0850 AC: 5781 AN: 67994

Other (OTH) AF: 0.106 AC: 223 AN: 2112

Alfa AF: 0.0877 Hom.: 1348

Bravo AF: 0.102

Asia WGS AF: 0.0870 AC: 302 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.020
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: rs11076174; hg19: chr16-57003146; COSMIC: COSV52364539;