chr16-56978024-C-T

Variant names:

• chr16-56978024-C-T
• rs891144
• NM_000078.3:c.982-67C>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.982-67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 1,578,790 control chromosomes in the GnomAD database, including 2,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (882 hom., cov: 32)
  • Exomes 𝑓: 0.024 (1462 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.12
• Publications: 10 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 16-56978024-C-T is Benign according to our data. Variant chr16-56978024-C-T is described in ClinVar as Benign. ClinVar VariationId is 1228339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 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.982-67C>T		intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.802-67C>T		intron	N/A	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.982-67C>T		intron	N/A	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.802-67C>T		intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.1090-67C>T		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10936 AN: 152102 Hom.: 879 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0932

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0608

GnomAD4 exome AF: 0.0237 AC: 33771 AN: 1426570 Hom.: 1462 AF XY: 0.0236 AC XY: 16680 AN XY: 707036

African (AFR) AF: 0.190 AC: 6209 AN: 32656

American (AMR) AF: 0.118 AC: 5010 AN: 42608

Ashkenazi Jewish (ASJ) AF: 0.00624 AC: 152 AN: 24354

East Asian (EAS) AF: 0.118 AC: 4651 AN: 39348

South Asian (SAS) AF: 0.0495 AC: 4084 AN: 82568

European-Finnish (FIN) AF: 0.0172 AC: 883 AN: 51272

Middle Eastern (MID) AF: 0.0145 AC: 64 AN: 4412

European-Non Finnish (NFE) AF: 0.00991 AC: 10802 AN: 1090526

Other (OTH) AF: 0.0326 AC: 1916 AN: 58826

GnomAD4 genome AF: 0.0721 AC: 10969 AN: 152220 Hom.: 882 Cov.: 32 AF XY: 0.0721 AC XY: 5370 AN XY: 74442

African (AFR) AF: 0.183 AC: 7613 AN: 41526

American (AMR) AF: 0.0937 AC: 1432 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.125 AC: 648 AN: 5166

South Asian (SAS) AF: 0.0532 AC: 257 AN: 4830

European-Finnish (FIN) AF: 0.0164 AC: 174 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0103 AC: 698 AN: 68012

Other (OTH) AF: 0.0620 AC: 131 AN: 2112

Alfa AF: 0.0301 Hom.: 189

Bravo AF: 0.0851

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.064
DANN	Benign	0.59
PhyloP100		-3.1
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: rs891144; hg19: chr16-57011936; COSMIC: COSV52363520; COSMIC: COSV52363520;