rs9930761

Variant names:

• chr16-56973280-T-C
• rs9930761
• NM_000078.3:c.751-51T>C

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.751-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 1,595,658 control chromosomes in the GnomAD database, including 3,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (461 hom., cov: 32)
  • Exomes 𝑓: 0.063 (3126 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.605
• Publications: 24 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 16-56973280-T-C is Benign according to our data. Variant chr16-56973280-T-C is described in ClinVar as Benign. ClinVar VariationId is 1297243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.751-51T>C		intron_variant	Intron 8 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.750+1197T>C		intron_variant	Intron 8 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.751-51T>C		intron_variant	Intron 8 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.750+1197T>C		intron_variant	Intron 8 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.556-51T>C		intron_variant	Intron 8 of 15	5		ENSP00000456276.1
CETP	ENST00000569082.1	n.853-51T>C		intron_variant	Intron 8 of 8	5

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10889 AN: 152162 Hom.: 459 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.0665

GnomAD2 exomes AF: 0.0594 AC: 14705 AN: 247614 AF XY: 0.0596

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.0337

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.000491

Gnomad FIN exome AF: 0.0436

Gnomad NFE exome AF: 0.0662

Gnomad OTH exome AF: 0.0724

GnomAD4 exome AF: 0.0627 AC: 90556 AN: 1443378 Hom.: 3126 Cov.: 29 AF XY: 0.0627 AC XY: 45035 AN XY: 718822

African (AFR) AF: 0.113 AC: 3726 AN: 33106

American (AMR) AF: 0.0351 AC: 1566 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3361 AN: 26024

East Asian (EAS) AF: 0.000354 AC: 14 AN: 39564

South Asian (SAS) AF: 0.0593 AC: 5097 AN: 85922

European-Finnish (FIN) AF: 0.0479 AC: 2486 AN: 51940

Middle Eastern (MID) AF: 0.0828 AC: 474 AN: 5726

European-Non Finnish (NFE) AF: 0.0639 AC: 70074 AN: 1096662

Other (OTH) AF: 0.0629 AC: 3758 AN: 59784

GnomAD4 genome AF: 0.0716 AC: 10900 AN: 152280 Hom.: 461 Cov.: 32 AF XY: 0.0677 AC XY: 5037 AN XY: 74456

African (AFR) AF: 0.108 AC: 4501 AN: 41558

American (AMR) AF: 0.0465 AC: 712 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5190

South Asian (SAS) AF: 0.0609 AC: 294 AN: 4824

European-Finnish (FIN) AF: 0.0386 AC: 410 AN: 10616

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0628 AC: 4271 AN: 68012

Other (OTH) AF: 0.0687 AC: 145 AN: 2112

Alfa AF: 0.0690 Hom.: 1436

Bravo AF: 0.0743

Asia WGS AF: 0.0360 AC: 125 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

This variant is associated with the following publications: (PMID: 24393849, 22403620) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.90
PhyloP100		-0.60
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: rs9930761; hg19: chr16-57007192;