rs289714

Variant names:

• chr16-56973539-G-A
• rs289714
• NM_000078.3:c.930+29G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-56973539-G-A
• chr16-56973539-G-C
• chr16-56973539-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000078.3(CETP):​c.930+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,612,824 control chromosomes in the GnomAD database, including 515,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39930 hom., cov: 31)
  • Exomes 𝑓: 0.80 (475636 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.996
• Publications: 56 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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-56973539-G-A is Benign according to our data. Variant chr16-56973539-G-A is described in ClinVar as Benign. ClinVar VariationId is 1181918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.930+29G>A		intron_variant	Intron 9 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.750+1456G>A		intron_variant	Intron 8 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.930+29G>A		intron_variant	Intron 9 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.750+1456G>A		intron_variant	Intron 8 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.735+29G>A		intron_variant	Intron 9 of 15	5		ENSP00000456276.1
CETP	ENST00000569082.1	n.*171G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107323 AN: 152000 Hom.: 39919 Cov.: 31

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.718

GnomAD2 exomes AF: 0.763 AC: 190435 AN: 249608 AF XY: 0.772

Gnomad AFR exome AF: 0.457

Gnomad AMR exome AF: 0.661

Gnomad ASJ exome AF: 0.841

Gnomad EAS exome AF: 0.721

Gnomad FIN exome AF: 0.842

Gnomad NFE exome AF: 0.822

Gnomad OTH exome AF: 0.798

GnomAD4 exome AF: 0.804 AC: 1174662 AN: 1460704 Hom.: 475636 Cov.: 37 AF XY: 0.805 AC XY: 584706 AN XY: 726658

African (AFR) AF: 0.457 AC: 15283 AN: 33462

American (AMR) AF: 0.663 AC: 29582 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 21938 AN: 26124

East Asian (EAS) AF: 0.763 AC: 30283 AN: 39684

South Asian (SAS) AF: 0.761 AC: 65589 AN: 86204

European-Finnish (FIN) AF: 0.843 AC: 44783 AN: 53122

Middle Eastern (MID) AF: 0.793 AC: 4532 AN: 5716

European-Non Finnish (NFE) AF: 0.823 AC: 915176 AN: 1111430

Other (OTH) AF: 0.787 AC: 47496 AN: 60372

GnomAD4 genome AF: 0.706 AC: 107365 AN: 152120 Hom.: 39930 Cov.: 31 AF XY: 0.707 AC XY: 52562 AN XY: 74362

African (AFR) AF: 0.463 AC: 19179 AN: 41450

American (AMR) AF: 0.679 AC: 10371 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2911 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3792 AN: 5168

South Asian (SAS) AF: 0.767 AC: 3696 AN: 4816

European-Finnish (FIN) AF: 0.851 AC: 9026 AN: 10608

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55834 AN: 68012

Other (OTH) AF: 0.719 AC: 1521 AN: 2114

Alfa AF: 0.786 Hom.: 82316

Bravo AF: 0.681

Asia WGS AF: 0.743 AC: 2585 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.51
PhyloP100		-1.0
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: rs289714; hg19: chr16-57007451; COSMIC: COSV52361859; COSMIC: COSV52361859;