rs289717

Variant names:

• chr16-56975476-G-A
• rs289717
• NM_000078.3:c.981+325G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-56975476-G-A
• chr16-56975476-G-C
• chr16-56975476-G-T

Variant summary

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

The NM_000078.3(CETP):​c.981+325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,106 control chromosomes in the GnomAD database, including 7,010 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 0.29 (7010 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 14 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.981+325G>A		intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.801+325G>A		intron	N/A	NP_001273014.1	A0A0S2Z3I8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	ENST00000200676.8	TSL:1 MANE Select	c.981+325G>A		intron	N/A	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.801+325G>A		intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.981+325G>A		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44338 AN: 151988 Hom.: 7010 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.292 AC: 44346 AN: 152106 Hom.: 7010 Cov.: 32 AF XY: 0.291 AC XY: 21626 AN XY: 74360

African (AFR) AF: 0.178 AC: 7386 AN: 41482

American (AMR) AF: 0.310 AC: 4736 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3472

East Asian (EAS) AF: 0.433 AC: 2239 AN: 5166

South Asian (SAS) AF: 0.236 AC: 1137 AN: 4826

European-Finnish (FIN) AF: 0.344 AC: 3639 AN: 10586

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23116 AN: 67980

Other (OTH) AF: 0.317 AC: 670 AN: 2114

Alfa AF: 0.327 Hom.: 31620

Bravo AF: 0.286

Asia WGS AF: 0.319 AC: 1110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.53
PhyloP100		0.38
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: rs289717; hg19: chr16-57009388;