chr16-56970977-G-A

Variant names:

• chr16-56970977-G-A
• rs7205804
• NM_000078.3:c.528-56G>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.528-56G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,533,662 control chromosomes in the GnomAD database, including 138,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10415 hom., cov: 32)
  • Exomes 𝑓: 0.43 (127982 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.17
• Publications: 67 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=-0.86).
• BP6: Variant 16-56970977-G-A is Benign according to our data. Variant chr16-56970977-G-A is described in ClinVar as Benign. ClinVar VariationId is 1249684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.469 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.528-56G>A		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.528-56G>A		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.528-56G>A		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.528-56G>A		intron	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.333-56G>A		intron	N/A	ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52623 AN: 151932 Hom.: 10421 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.427 AC: 589587 AN: 1381612 Hom.: 127982 AF XY: 0.430 AC XY: 297635 AN XY: 691882

African (AFR) AF: 0.146 AC: 4663 AN: 31850

American (AMR) AF: 0.367 AC: 16281 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 9969 AN: 25672

East Asian (EAS) AF: 0.310 AC: 12180 AN: 39280

South Asian (SAS) AF: 0.493 AC: 41690 AN: 84560

European-Finnish (FIN) AF: 0.420 AC: 22253 AN: 52958

Middle Eastern (MID) AF: 0.398 AC: 2253 AN: 5666

European-Non Finnish (NFE) AF: 0.439 AC: 456616 AN: 1039476

Other (OTH) AF: 0.410 AC: 23682 AN: 57742

GnomAD4 genome AF: 0.346 AC: 52614 AN: 152050 Hom.: 10415 Cov.: 32 AF XY: 0.348 AC XY: 25897 AN XY: 74318

African (AFR) AF: 0.151 AC: 6273 AN: 41526

American (AMR) AF: 0.343 AC: 5244 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3468

East Asian (EAS) AF: 0.303 AC: 1563 AN: 5158

South Asian (SAS) AF: 0.485 AC: 2333 AN: 4808

European-Finnish (FIN) AF: 0.422 AC: 4463 AN: 10566

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.442 AC: 30018 AN: 67932

Other (OTH) AF: 0.341 AC: 719 AN: 2110

Alfa AF: 0.406 Hom.: 40360

Bravo AF: 0.328

Asia WGS AF: 0.368 AC: 1281 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.63
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7205804; hg19: chr16-57004889; COSMIC: COSV52362249;