16-56962299-G-A

Variant names:

• chr16-56962299-G-A
• rs711752
• NM_000078.3:c.118+202G>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+202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 737,362 control chromosomes in the GnomAD database, including 65,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11865 hom., cov: 31)
  • Exomes 𝑓: 0.42 (53322 hom.)
• Consequence: CETP NM_000078.3 intron
• Scores: Splicing: ADA: 0.0001408
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01
• Publications: 47 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=-0.82).
• BP6: Variant 16-56962299-G-A is Benign according to our data. Variant chr16-56962299-G-A is described in ClinVar as Benign. ClinVar VariationId is 1255212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.118+202G>A		intron_variant	Intron 1 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.118+202G>A		intron_variant	Intron 1 of 14		NP_001273014.1
CETP	XM_006721124.4	c.118+202G>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+202G>A		intron_variant	Intron 1 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.118+202G>A		intron_variant	Intron 1 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.-78+3G>A		splice_region_variant, intron_variant	Intron 1 of 15	5		ENSP00000456276.1
CETP	ENST00000569082.1	n.116+202G>A		intron_variant	Intron 1 of 8	5

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58532 AN: 151832 Hom.: 11855 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.424 AC: 248464 AN: 585410 Hom.: 53322 Cov.: 3 AF XY: 0.428 AC XY: 136870 AN XY: 319762

African (AFR) AF: 0.258 AC: 4429 AN: 17156

American (AMR) AF: 0.463 AC: 18791 AN: 40622

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 7495 AN: 19942

East Asian (EAS) AF: 0.390 AC: 13590 AN: 34822

South Asian (SAS) AF: 0.471 AC: 31662 AN: 67266

European-Finnish (FIN) AF: 0.447 AC: 16102 AN: 36040

Middle Eastern (MID) AF: 0.393 AC: 1580 AN: 4024

European-Non Finnish (NFE) AF: 0.425 AC: 141819 AN: 334018

Other (OTH) AF: 0.412 AC: 12996 AN: 31520

GnomAD4 genome AF: 0.386 AC: 58585 AN: 151952 Hom.: 11865 Cov.: 31 AF XY: 0.391 AC XY: 29016 AN XY: 74246

African (AFR) AF: 0.265 AC: 10992 AN: 41464

American (AMR) AF: 0.419 AC: 6398 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1333 AN: 3472

East Asian (EAS) AF: 0.377 AC: 1940 AN: 5150

South Asian (SAS) AF: 0.463 AC: 2224 AN: 4808

European-Finnish (FIN) AF: 0.454 AC: 4784 AN: 10536

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29517 AN: 67958

Other (OTH) AF: 0.381 AC: 803 AN: 2108

Alfa AF: 0.339 Hom.: 2279

Bravo AF: 0.376

Asia WGS AF: 0.410 AC: 1428 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		1.0
PromoterAI		0.054	Neutral
Mutation Taster		=80/20	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.51		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.51		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs711752; hg19: chr16-56996211; COSMIC: COSV52362751;