NM_000078.3:c.*84G>A

Variant names:

• chr16-56983750-G-A
• rs1801706
• NM_000078.3:c.*84G>A

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.*84G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,303,282 control chromosomes in the GnomAD database, including 20,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2198 hom., cov: 32)
  • Exomes 𝑓: 0.17 (18081 hom.)
• Consequence: CETP NM_000078.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.20
• 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: 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=-0.9).
• BP6: Variant 16-56983750-G-A is Benign according to our data. Variant chr16-56983750-G-A is described in ClinVar as Benign. ClinVar VariationId is 320000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.*84G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.*84G>A		3_prime_UTR_variant	Exon 15 of 15		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.*84G>A		3_prime_UTR_variant	Exon 16 of 16	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.*84G>A		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.*84G>A		3_prime_UTR_variant	Exon 16 of 16	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25083 AN: 152024 Hom.: 2198 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0992

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.174 AC: 199929 AN: 1151140 Hom.: 18081 Cov.: 16 AF XY: 0.175 AC XY: 102613 AN XY: 587044

African (AFR) AF: 0.153 AC: 4181 AN: 27346

American (AMR) AF: 0.0850 AC: 3757 AN: 44218

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 6793 AN: 24248

East Asian (EAS) AF: 0.106 AC: 4040 AN: 38214

South Asian (SAS) AF: 0.189 AC: 15069 AN: 79528

European-Finnish (FIN) AF: 0.215 AC: 11250 AN: 52376

Middle Eastern (MID) AF: 0.196 AC: 1022 AN: 5218

European-Non Finnish (NFE) AF: 0.175 AC: 144867 AN: 829830

Other (OTH) AF: 0.178 AC: 8950 AN: 50162

GnomAD4 genome AF: 0.165 AC: 25095 AN: 152142 Hom.: 2198 Cov.: 32 AF XY: 0.164 AC XY: 12174 AN XY: 74362

African (AFR) AF: 0.148 AC: 6160 AN: 41516

American (AMR) AF: 0.111 AC: 1691 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3470

East Asian (EAS) AF: 0.0990 AC: 513 AN: 5180

South Asian (SAS) AF: 0.184 AC: 888 AN: 4814

European-Finnish (FIN) AF: 0.211 AC: 2225 AN: 10570

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11958 AN: 67974

Other (OTH) AF: 0.175 AC: 370 AN: 2112

Alfa AF: 0.169 Hom.: 8678

Bravo AF: 0.156

Asia WGS AF: 0.164 AC: 568 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Sep 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 8830936, 27768712) -

Hyperalphalipoproteinemia 1 Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.026
DANN	Benign	0.47
PhyloP100		-5.2
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: rs1801706; hg19: chr16-57017662;