rs289741

Variant names:

• chr16-56983562-G-A
• rs289741
• NM_000078.3:c.1408-30G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-56983562-G-A
• chr16-56983562-G-C
• chr16-56983562-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.1408-30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,612,930 control chromosomes in the GnomAD database, including 369,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.61 (29951 hom., cov: 32)
  • Exomes 𝑓: 0.68 (339994 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.788
• Publications: 34 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-56983562-G-A is Benign according to our data. Variant chr16-56983562-G-A is described in ClinVar as Benign. ClinVar VariationId is 1285774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.692 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.1408-30G>A		intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.1228-30G>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.1408-30G>A		intron	N/A	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.1228-30G>A		intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.1516-30G>A		intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93249 AN: 151896 Hom.: 29926 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.649

GnomAD2 exomes AF: 0.661 AC: 166087 AN: 251130 AF XY: 0.664

Gnomad AFR exome AF: 0.420

Gnomad AMR exome AF: 0.701

Gnomad ASJ exome AF: 0.596

Gnomad EAS exome AF: 0.694

Gnomad FIN exome AF: 0.658

Gnomad NFE exome AF: 0.699

Gnomad OTH exome AF: 0.651

GnomAD4 exome AF: 0.680 AC: 993571 AN: 1460916 Hom.: 339994 Cov.: 38 AF XY: 0.678 AC XY: 493011 AN XY: 726812

African (AFR) AF: 0.411 AC: 13768 AN: 33464

American (AMR) AF: 0.702 AC: 31385 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 15488 AN: 26130

East Asian (EAS) AF: 0.647 AC: 25662 AN: 39692

South Asian (SAS) AF: 0.614 AC: 52918 AN: 86234

European-Finnish (FIN) AF: 0.654 AC: 34920 AN: 53384

Middle Eastern (MID) AF: 0.616 AC: 3547 AN: 5754

European-Non Finnish (NFE) AF: 0.698 AC: 775892 AN: 1111186

Other (OTH) AF: 0.663 AC: 39991 AN: 60350

GnomAD4 genome AF: 0.614 AC: 93318 AN: 152014 Hom.: 29951 Cov.: 32 AF XY: 0.614 AC XY: 45607 AN XY: 74292

African (AFR) AF: 0.425 AC: 17621 AN: 41418

American (AMR) AF: 0.702 AC: 10735 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2052 AN: 3470

East Asian (EAS) AF: 0.690 AC: 3561 AN: 5164

South Asian (SAS) AF: 0.607 AC: 2926 AN: 4820

European-Finnish (FIN) AF: 0.659 AC: 6980 AN: 10586

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47398 AN: 67948

Other (OTH) AF: 0.650 AC: 1370 AN: 2108

Alfa AF: 0.656 Hom.: 18286

Bravo AF: 0.608

Asia WGS AF: 0.621 AC: 2161 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.79
DANN	Benign	0.83
PhyloP100		-0.79
BranchPoint Hunter		2.0
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: rs289741; hg19: chr16-57017474;