rs9923854

Positions:

• chr16-56983090-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 1222632.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56983090-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.1322-236T>G		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.1142-236T>G		intron_variant			NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.1322-236T>G		intron_variant		1	NM_000078.3	ENSP00000200676	P1
CETP	ENST00000379780.6	c.1142-236T>G		intron_variant		1		ENSP00000369106
CETP	ENST00000566128.1	c.1127-236T>G		intron_variant		5		ENSP00000456276
CETP	ENST00000650358.1	n.1720-236T>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0992

Alfa AF: 0.101 Hom.: 1141

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs9923854; hg19: chr16-57017002;