16-56974375-A-G

Variant names:

• chr16-56974375-A-G
• rs158617
• NM_000078.3:c.931-726A>G

Variant summary

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

The NM_000078.3(CETP):​c.931-726A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,162 control chromosomes in the GnomAD database, including 48,904 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 0.80 (48904 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.867 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.931-726A>G		intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.751-726A>G		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.931-726A>G		intron	N/A	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.751-726A>G		intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.931-726A>G		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 121046 AN: 152042 Hom.: 48885 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.796 AC: 121115 AN: 152162 Hom.: 48904 Cov.: 32 AF XY: 0.791 AC XY: 58848 AN XY: 74400

African (AFR) AF: 0.686 AC: 28439 AN: 41456

American (AMR) AF: 0.756 AC: 11557 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3059 AN: 3472

East Asian (EAS) AF: 0.661 AC: 3417 AN: 5172

South Asian (SAS) AF: 0.715 AC: 3448 AN: 4820

European-Finnish (FIN) AF: 0.855 AC: 9074 AN: 10608

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59414 AN: 68030

Other (OTH) AF: 0.816 AC: 1724 AN: 2112

Alfa AF: 0.836 Hom.: 6650

Bravo AF: 0.782

Asia WGS AF: 0.695 AC: 2418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		-0.58
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: rs158617; hg19: chr16-57008287;