16-56975283-T-G

Variant names:

• chr16-56975283-T-G
• rs2303789
• NM_000078.3:c.981+132T>G

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.981+132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 783,678 control chromosomes in the GnomAD database, including 769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (189 hom., cov: 32)
  • Exomes 𝑓: 0.019 (580 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.582
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-56975283-T-G is Benign according to our data. Variant chr16-56975283-T-G is described in ClinVar as Benign. ClinVar VariationId is 1291729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 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.981+132T>G		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.801+132T>G		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.981+132T>G		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.801+132T>G		intron	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.786+132T>G		intron	N/A	ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5098 AN: 152136 Hom.: 186 Cov.: 32

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0748

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.0302

GnomAD4 exome AF: 0.0193 AC: 12170 AN: 631424 Hom.: 580 AF XY: 0.0187 AC XY: 6205 AN XY: 332704

African (AFR) AF: 0.0669 AC: 1141 AN: 17060

American (AMR) AF: 0.104 AC: 3329 AN: 32072

Ashkenazi Jewish (ASJ) AF: 0.000563 AC: 10 AN: 17766

East Asian (EAS) AF: 0.123 AC: 3992 AN: 32524

South Asian (SAS) AF: 0.0277 AC: 1663 AN: 60134

European-Finnish (FIN) AF: 0.0140 AC: 610 AN: 43420

Middle Eastern (MID) AF: 0.00594 AC: 24 AN: 4042

European-Non Finnish (NFE) AF: 0.00187 AC: 734 AN: 391754

Other (OTH) AF: 0.0204 AC: 667 AN: 32652

GnomAD4 genome AF: 0.0336 AC: 5121 AN: 152254 Hom.: 189 Cov.: 32 AF XY: 0.0355 AC XY: 2646 AN XY: 74446

African (AFR) AF: 0.0671 AC: 2786 AN: 41530

American (AMR) AF: 0.0754 AC: 1153 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.133 AC: 690 AN: 5184

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4828

European-Finnish (FIN) AF: 0.0142 AC: 151 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00193 AC: 131 AN: 68022

Other (OTH) AF: 0.0318 AC: 67 AN: 2106

Alfa AF: 0.0202 Hom.: 15

Bravo AF: 0.0425

Asia WGS AF: 0.0810 AC: 279 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	-0.98
CADD	Benign	0.82
DANN	Benign	0.42
PhyloP100		-0.58
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: rs2303789; hg19: chr16-57009195; COSMIC: COSV52364939; COSMIC: COSV52364939;