chr16-56975857-T-A

Variant names:

• chr16-56975857-T-A
• rs736274
• NM_000078.3:c.981+706T>A

Variant summary

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

The NM_000078.3(CETP):​c.981+706T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 152,090 control chromosomes in the GnomAD database, including 803 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 0.089 (803 hom., cov: 31)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.981+706T>A		intron_variant	Intron 10 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.801+706T>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.981+706T>A		intron_variant	Intron 10 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.801+706T>A		intron_variant	Intron 9 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.786+706T>A		intron_variant	Intron 10 of 15	5		ENSP00000456276.1

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 13584 AN: 151972 Hom.: 804 Cov.: 31

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0883

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0907

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

GnomAD4 genome AF: 0.0892 AC: 13574 AN: 152090 Hom.: 803 Cov.: 31 AF XY: 0.0924 AC XY: 6866 AN XY: 74328

African (AFR) AF: 0.0283 AC: 1174 AN: 41512

American (AMR) AF: 0.0883 AC: 1351 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 352 AN: 3470

East Asian (EAS) AF: 0.0920 AC: 475 AN: 5162

South Asian (SAS) AF: 0.173 AC: 830 AN: 4802

European-Finnish (FIN) AF: 0.127 AC: 1348 AN: 10574

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7696 AN: 67966

Other (OTH) AF: 0.0888 AC: 187 AN: 2106

Alfa AF: 0.0963 Hom.: 103

Bravo AF: 0.0826

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.85
PhyloP100		-0.088
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: rs736274; hg19: chr16-57009769;