16-56983750-G-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: Labcorp Genetics (formerly Invitae), Orphanet

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.

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.*84G>A		3_prime_UTR	Exon 16 of 16	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.*84G>A		3_prime_UTR	Exon 15 of 15	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.*84G>A		3_prime_UTR	Exon 16 of 16	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.*84G>A		3_prime_UTR	Exon 15 of 15	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.*84G>A		3_prime_UTR	Exon 17 of 17	ENSP00000528341.1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hyperalphalipoproteinemia 1 (1)

Computational scores

Source: dbNSFP v4.9

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;