chr16-56962192-C-A

Variant names:

• chr16-56962192-C-A
• rs17231534
• NM_000078.3:c.118+95C>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.118+95C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,043,986 control chromosomes in the GnomAD database, including 2,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (472 hom., cov: 32)
  • Exomes 𝑓: 0.053 (1593 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.353
• Publications: 7 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 16-56962192-C-A is Benign according to our data. Variant chr16-56962192-C-A is described in ClinVar as [Benign]. Clinvar id is 1282916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.118+95C>A		intron_variant	Intron 1 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.118+95C>A		intron_variant	Intron 1 of 14		NP_001273014.1
CETP	XM_006721124.4	c.118+95C>A		intron_variant	Intron 1 of 8		XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.118+95C>A		intron_variant	Intron 1 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.118+95C>A		intron_variant	Intron 1 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.-182C>A		5_prime_UTR_variant	Exon 1 of 16	5		ENSP00000456276.1
CETP	ENST00000569082.1	n.116+95C>A		intron_variant	Intron 1 of 8	5

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10836 AN: 152126 Hom.: 471 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0586

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0718

GnomAD4 exome AF: 0.0529 AC: 47185 AN: 891742 Hom.: 1593 Cov.: 12 AF XY: 0.0540 AC XY: 25194 AN XY: 466458

African (AFR) AF: 0.122 AC: 2744 AN: 22492

American (AMR) AF: 0.0533 AC: 2331 AN: 43736

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3095 AN: 22610

East Asian (EAS) AF: 0.0618 AC: 2293 AN: 37124

South Asian (SAS) AF: 0.0847 AC: 6295 AN: 74278

European-Finnish (FIN) AF: 0.0492 AC: 2116 AN: 42978

Middle Eastern (MID) AF: 0.0922 AC: 431 AN: 4674

European-Non Finnish (NFE) AF: 0.0420 AC: 25262 AN: 602186

Other (OTH) AF: 0.0628 AC: 2618 AN: 41664

GnomAD4 genome AF: 0.0712 AC: 10844 AN: 152244 Hom.: 472 Cov.: 32 AF XY: 0.0707 AC XY: 5261 AN XY: 74442

African (AFR) AF: 0.121 AC: 5039 AN: 41534

American (AMR) AF: 0.0587 AC: 898 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3472

East Asian (EAS) AF: 0.0621 AC: 322 AN: 5182

South Asian (SAS) AF: 0.0845 AC: 408 AN: 4830

European-Finnish (FIN) AF: 0.0502 AC: 532 AN: 10596

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0427 AC: 2904 AN: 68014

Other (OTH) AF: 0.0743 AC: 157 AN: 2112

Alfa AF: 0.0491 Hom.: 200

Bravo AF: 0.0736

Asia WGS AF: 0.0780 AC: 273 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

- -

Sep 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.74
PhyloP100		-0.35
PromoterAI		-0.0084	Neutral
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: rs17231534; hg19: chr16-56996104;