16-56981633-C-T

Variant names:

• chr16-56981633-C-T
• rs1800774
• NM_000078.3:c.1215-14C>T

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.1215-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,610,056 control chromosomes in the GnomAD database, including 95,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8055 hom., cov: 32)
  • Exomes 𝑓: 0.34 (87462 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.579
• Publications: 40 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=-0.77).
• BP6: Variant 16-56981633-C-T is Benign according to our data. Variant chr16-56981633-C-T is described in ClinVar as Benign. ClinVar VariationId is 319995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 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.1215-14C>T		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.1035-14C>T		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.1215-14C>T		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.1035-14C>T		intron	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.1020-14C>T		intron	N/A	ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48282 AN: 151982 Hom.: 8051 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.315

GnomAD2 exomes AF: 0.320 AC: 80337 AN: 251354 AF XY: 0.324

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.135

Gnomad FIN exome AF: 0.300

Gnomad NFE exome AF: 0.359

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.342 AC: 498030 AN: 1457956 Hom.: 87462 Cov.: 34 AF XY: 0.342 AC XY: 247775 AN XY: 725516

African (AFR) AF: 0.268 AC: 8945 AN: 33414

American (AMR) AF: 0.329 AC: 14693 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 7323 AN: 26106

East Asian (EAS) AF: 0.0983 AC: 3903 AN: 39690

South Asian (SAS) AF: 0.333 AC: 28731 AN: 86174

European-Finnish (FIN) AF: 0.304 AC: 16244 AN: 53376

Middle Eastern (MID) AF: 0.288 AC: 1656 AN: 5756

European-Non Finnish (NFE) AF: 0.358 AC: 396681 AN: 1108466

Other (OTH) AF: 0.330 AC: 19854 AN: 60254

GnomAD4 genome AF: 0.318 AC: 48299 AN: 152100 Hom.: 8055 Cov.: 32 AF XY: 0.314 AC XY: 23362 AN XY: 74364

African (AFR) AF: 0.269 AC: 11180 AN: 41486

American (AMR) AF: 0.332 AC: 5077 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3466

East Asian (EAS) AF: 0.127 AC: 658 AN: 5194

South Asian (SAS) AF: 0.313 AC: 1510 AN: 4828

European-Finnish (FIN) AF: 0.304 AC: 3211 AN: 10568

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24688 AN: 67962

Other (OTH) AF: 0.311 AC: 657 AN: 2114

Alfa AF: 0.324 Hom.: 6164

Bravo AF: 0.314

Asia WGS AF: 0.212 AC: 740 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hyperalphalipoproteinemia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.4
DANN	Benign	0.70
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1800774; hg19: chr16-57015545; COSMIC: COSV52361521;