16-56983750-G-C

Variant names:

• chr16-56983750-G-C
• rs1801706
• NM_000078.3:c.*84G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000078.3(CETP):​c.*84G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000174 in 1,152,642 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: CETP NM_000078.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.20
• Publications: 39 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.*84G>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.*84G>C		3_prime_UTR_variant	Exon 15 of 15		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.*84G>C		3_prime_UTR_variant	Exon 16 of 16	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.*84G>C		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.*84G>C		3_prime_UTR_variant	Exon 16 of 16	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000174 AC: 2 AN: 1152642 Hom.: 0 Cov.: 16 AF XY: 0.00000170 AC XY: 1 AN XY: 587844

African (AFR) AF: 0.00 AC: 0 AN: 27372

American (AMR) AF: 0.00 AC: 0 AN: 44226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24264

East Asian (EAS) AF: 0.00 AC: 0 AN: 38228

South Asian (SAS) AF: 0.00 AC: 0 AN: 79560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5222

European-Non Finnish (NFE) AF: 0.00000241 AC: 2 AN: 831172

Other (OTH) AF: 0.00 AC: 0 AN: 50196

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 8678

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.010
DANN	Benign	0.37
PhyloP100		-5.2

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: rs1801706; hg19: chr16-57017662;