16-56971567-C-G

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_000078.3(CETP):c.658+186C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 0 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: Likely_benign. The variant received -2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (base 0.0001, raised to 0.000102 by highest known P/LP ClinVar AF 0.000102) — PM2 moderate.
	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).

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>G	intron	Intron 7 of 15	Prot: NP_000069.2 UniProt:
	CETP NM_001286085.2		c.658+186C>G	intron	Intron 7 of 14	Prot: NP_001273014.1 UniProt:

CETP NM_000078.3

MANE Select

HGVSc / HGVSpc.658+186C>G

Exon rankIntron 7 of 15

intron

Prot: NP_000069.2UniProt: A0A0S2Z3F6P11597-1

CETP NM_001286085.2

HGVSc / HGVSpc.658+186C>G

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>G	intron	Intron 7 of 15	Prot: ENSP00000200676.3 UniProt:
	CETP ENST00000379780.6	TSL:1	c.658+186C>G	intron	Intron 7 of 14	Prot: ENSP00000369106.2 UniProt:
	CETP ENST00000858282.1		c.658+186C>G	intron	Intron 7 of 16	Prot: ENSP00000528341.1 UniProt:

CETP ENST00000200676.8

TSL:1MANE Select

HGVSc / HGVSpc.658+186C>G

Exon rankIntron 7 of 15

intron

Prot: ENSP00000200676.3UniProt: P11597-1

CETP ENST00000379780.6

TSL:1

HGVSc / HGVSpc.658+186C>G

Exon rankIntron 7 of 14

intron

Prot: ENSP00000369106.2UniProt: P11597-2

CETP ENST00000858282.1

HGVSc / HGVSpc.658+186C>G

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 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	7.8
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.7
DANN	Benign	0.73
GPN-Star LLR	N/A	0.68
GPN-Star score	N/A	-0.68
PhyloP100	Benign	-0.059

Showing 7 of 7 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