16-56962367-C-T

Position:

• chr16-56962367-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000078.3(CETP):​c.118+270C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 686,174 control chromosomes in the GnomAD database, including 235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (37 hom., cov: 32)
  • Exomes 𝑓: 0.022 (198 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.175

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-56962367-C-T is Benign according to our data. Variant chr16-56962367-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1214705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2863/152100) while in subpopulation NFE AF= 0.0307 (2087/67992). AF 95% confidence interval is 0.0296. There are 37 homozygotes in gnomad4. There are 1265 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CETP	NM_000078.3	c.118+270C>T		intron_variant		ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.118+270C>T		intron_variant			NP_001273014.1
CETP	XM_006721124.4	c.118+270C>T		intron_variant			XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.118+270C>T		intron_variant		1	NM_000078.3	ENSP00000200676	P1
CETP	ENST00000379780.6	c.118+270C>T		intron_variant		1		ENSP00000369106
CETP	ENST00000566128.1	c.-78+71C>T		intron_variant		5		ENSP00000456276
CETP	ENST00000569082.1	n.116+270C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2862 AN: 151982 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.00578

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.00482

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.0194 AC: 4415 AN: 228036 Hom.: 67 AF XY: 0.0196 AC XY: 2471 AN XY: 125972

Gnomad AFR exome AF: 0.00577

Gnomad AMR exome AF: 0.0183

Gnomad ASJ exome AF: 0.00826

Gnomad EAS exome AF: 0.0000570

Gnomad SAS exome AF: 0.00352

Gnomad FIN exome AF: 0.00746

Gnomad NFE exome AF: 0.0315

Gnomad OTH exome AF: 0.0208

GnomAD4 exome AF: 0.0218 AC: 11632 AN: 534074 Hom.: 198 Cov.: 0 AF XY: 0.0211 AC XY: 6237 AN XY: 295136

Gnomad4 AFR exome AF: 0.00528

Gnomad4 AMR exome AF: 0.0191

Gnomad4 ASJ exome AF: 0.00938

Gnomad4 EAS exome AF: 0.0000348

Gnomad4 SAS exome AF: 0.00360

Gnomad4 FIN exome AF: 0.00914

Gnomad4 NFE exome AF: 0.0313

Gnomad4 OTH exome AF: 0.0235

GnomAD4 genome AF: 0.0188 AC: 2863 AN: 152100 Hom.: 37 Cov.: 32 AF XY: 0.0170 AC XY: 1265 AN XY: 74352

Gnomad4 AFR AF: 0.00576

Gnomad4 AMR AF: 0.0247

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00482

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0274 Hom.: 50

Bravo AF: 0.0208

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 07, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs5030708; hg19: chr16-56996279;