chr16-56983090-T-G

Variant names:

• chr16-56983090-T-G
• rs9923854
• NM_000078.3:c.1322-236T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000078.3(CETP):​c.1322-236T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,218 control chromosomes in the GnomAD database, including 865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (865 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24
• Publications: 16 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-56983090-T-G is Benign according to our data. Variant chr16-56983090-T-G is described in ClinVar as Benign. ClinVar VariationId is 1222632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 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.1322-236T>G		intron	N/A	NP_000069.2
	CETP	NM_001286085.2		c.1142-236T>G		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.1322-236T>G		intron	N/A	ENSP00000200676.3
	CETP	ENST00000379780.6	TSL:1	c.1142-236T>G		intron	N/A	ENSP00000369106.2
	CETP	ENST00000566128.1	TSL:5	c.1127-236T>G		intron	N/A	ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15334 AN: 152100 Hom.: 865 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0558

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0984

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15337 AN: 152218 Hom.: 865 Cov.: 33 AF XY: 0.0986 AC XY: 7337 AN XY: 74410

African (AFR) AF: 0.112 AC: 4641 AN: 41542

American (AMR) AF: 0.0666 AC: 1019 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0563 AC: 272 AN: 4832

European-Finnish (FIN) AF: 0.130 AC: 1374 AN: 10590

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6944 AN: 67982

Other (OTH) AF: 0.0992 AC: 210 AN: 2116

Alfa AF: 0.101 Hom.: 1440

Bravo AF: 0.0974

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 22, 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	-0.87
CADD	Benign	5.5
DANN	Benign	0.46
PhyloP100		1.2
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: rs9923854; hg19: chr16-57017002;