rs1532624

Variant names:

• chr16-56971567-C-A
• rs1532624
• NM_000078.3:c.658+186C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-56971567-C-A
• chr16-56971567-C-G
• chr16-56971567-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000078.3(CETP):​c.658+186C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,090 control chromosomes in the GnomAD database, including 10,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (10327 hom., cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0590
• Publications: 130 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-56971567-C-A is Benign according to our data. Variant chr16-56971567-C-A is described in ClinVar as Benign. ClinVar VariationId is 225955.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.46 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.658+186C>A		intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.658+186C>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.658+186C>A		intron	N/A	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.658+186C>A		intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.658+186C>A		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52339 AN: 151970 Hom.: 10332 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.344 AC: 52329 AN: 152090 Hom.: 10327 Cov.: 33 AF XY: 0.346 AC XY: 25749 AN XY: 74332

African (AFR) AF: 0.148 AC: 6163 AN: 41518

American (AMR) AF: 0.344 AC: 5256 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1352 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1461 AN: 5164

South Asian (SAS) AF: 0.476 AC: 2294 AN: 4820

European-Finnish (FIN) AF: 0.423 AC: 4465 AN: 10560

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30035 AN: 67986

Other (OTH) AF: 0.341 AC: 718 AN: 2108

Alfa AF: 0.404 Hom.: 42003

Bravo AF: 0.327

Asia WGS AF: 0.350 AC: 1219 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.6
DANN	Benign	0.79
PhyloP100		-0.059
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: rs1532624; hg19: chr16-57005479;