rs291044

Variant names:

• chr16-56977540-G-A
• rs291044
• NM_000078.3:c.982-551G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-56977540-G-A
• chr16-56977540-G-C

Variant summary

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

The NM_000078.3(CETP):​c.982-551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,016 control chromosomes in the GnomAD database, including 6,831 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 0.28 (6831 hom., cov: 32)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.982-551G>A		intron_variant	Intron 10 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.802-551G>A		intron_variant	Intron 9 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.982-551G>A		intron_variant	Intron 10 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.802-551G>A		intron_variant	Intron 9 of 14	1		ENSP00000369106.2
CETP	ENST00000650358.1	n.829G>A		non_coding_transcript_exon_variant	Exon 1 of 5
CETP	ENST00000566128.1	c.787-551G>A		intron_variant	Intron 10 of 15	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43282 AN: 151898 Hom.: 6830 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.285 AC: 43292 AN: 152016 Hom.: 6831 Cov.: 32 AF XY: 0.285 AC XY: 21153 AN XY: 74302

African (AFR) AF: 0.154 AC: 6393 AN: 41474

American (AMR) AF: 0.308 AC: 4707 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3468

East Asian (EAS) AF: 0.434 AC: 2238 AN: 5152

South Asian (SAS) AF: 0.236 AC: 1138 AN: 4824

European-Finnish (FIN) AF: 0.345 AC: 3641 AN: 10558

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23091 AN: 67944

Other (OTH) AF: 0.313 AC: 661 AN: 2112

Alfa AF: 0.306 Hom.: 2588

Bravo AF: 0.278

Asia WGS AF: 0.318 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.9
DANN	Benign	0.87
PhyloP100		0.75
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: rs291044; hg19: chr16-57011452;