16-56971567-C-A

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -14 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_StrongBP6_Moderate

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 cumulative frequency of 0.344 (AC=52,329) in the gnomAD database across 152,090 control chromosomes, including 10,327 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.46. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely 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: 132 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 Submitted by: Labcorp Genetics (formerly Invitae)

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -14 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BP6Reputable source reports benign		ClinVar 1-star benign — moderate (BP6); ClinVar germline classification: Benign/Likely Benign, 1 star(s).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4597 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000078.3. You can select a different transcript below to see updated classification 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	Intron 7 of 15	Prot: NP_000069.2 UniProt:
	CETP NM_001286085.2		c.658+186C>A	intron	Intron 7 of 14	Prot: NP_001273014.1 UniProt:

CETP NM_000078.3

MANE Select

HGVSc / HGVSpc.658+186C>A

Exon rankIntron 7 of 15

intron

Prot: NP_000069.2UniProt: A0A0S2Z3F6P11597-1

CETP NM_001286085.2

HGVSc / HGVSpc.658+186C>A

Exon rankIntron 7 of 14

intron

Prot: NP_001273014.1UniProt: A0A0S2Z3I8P11597-2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CETP ENST00000200676.8	TSL:1MANE Select	c.658+186C>A	intron	Intron 7 of 15	Prot: ENSP00000200676.3 UniProt:
	CETP ENST00000379780.6	TSL:1	c.658+186C>A	intron	Intron 7 of 14	Prot: ENSP00000369106.2 UniProt:
	CETP ENST00000858282.1		c.658+186C>A	intron	Intron 7 of 16	Prot: ENSP00000528341.1 UniProt:

CETP ENST00000200676.8

TSL:1MANE Select

HGVSc / HGVSpc.658+186C>A

Exon rankIntron 7 of 15

intron

Prot: ENSP00000200676.3UniProt: P11597-1

CETP ENST00000379780.6

TSL:1

HGVSc / HGVSpc.658+186C>A

Exon rankIntron 7 of 14

intron

Prot: ENSP00000369106.2UniProt: P11597-2

CETP ENST00000858282.1

HGVSc / HGVSpc.658+186C>A

Exon rankIntron 7 of 16

intron

Prot: ENSP00000528341.1UniProt: A0ACI8Q6I0

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.344	AC:52339	Hom:10332	AN:151970	Cov:33
GnomAD4 genome	AF: 0.344	AC:52329	Hom:10327	AN:152090	Cov:33
TOPMed (Bravo)	AF: 0.327	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.404	AC:209095	Hom:44066	AN:517896	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.339	AC:794	Hom:140	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.281	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.447	AC:134	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.350	AC:1219	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.271	AC:1964	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.403	AC:71	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.311	AC:38127	Hom:5952	AN:122754	Cov:
Turkish Variome	AF: 0.462	AC:714	Hom:167	AN:1544	Cov:
UK10K	AF: 0.453	AC:3423	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.298	AC:2671	Hom:399	AN:8960	Cov:

Showing 14 sources

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	6.6
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.6
DANN	Benign	0.79
GPN-Star LLR	N/A	0.66
GPN-Star score	N/A	-0.66
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.059

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs1532624;

hg19: chr16-57005479;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar