16-56977036-T-G

Variant names:

• chr16-56977036-T-G
• rs1968905
• NM_000078.3:c.982-1055T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000078.3(CETP):​c.982-1055T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 151,954 control chromosomes in the GnomAD database, including 46,843 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (46843 hom., cov: 30)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.982-1055T>G		intron_variant	Intron 10 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.802-1055T>G		intron_variant	Intron 9 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.982-1055T>G		intron_variant	Intron 10 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.802-1055T>G		intron_variant	Intron 9 of 14	1		ENSP00000369106.2
CETP	ENST00000650358.1	n.325T>G		non_coding_transcript_exon_variant	Exon 1 of 5
CETP	ENST00000566128.1	c.787-1055T>G		intron_variant	Intron 10 of 15	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 118986 AN: 151836 Hom.: 46801 Cov.: 30

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.784 AC: 119084 AN: 151954 Hom.: 46843 Cov.: 30 AF XY: 0.784 AC XY: 58233 AN XY: 74238

African (AFR) AF: 0.729 AC: 30196 AN: 41404

American (AMR) AF: 0.824 AC: 12591 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2413 AN: 3466

East Asian (EAS) AF: 0.781 AC: 4028 AN: 5158

South Asian (SAS) AF: 0.796 AC: 3818 AN: 4798

European-Finnish (FIN) AF: 0.787 AC: 8301 AN: 10552

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.813 AC: 55256 AN: 67988

Other (OTH) AF: 0.786 AC: 1656 AN: 2106

Alfa AF: 0.754 Hom.: 2618

Bravo AF: 0.783

Asia WGS AF: 0.763 AC: 2657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.29
PhyloP100		-0.53
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: rs1968905; hg19: chr16-57010948;