chr16-56962051-C-A

Variant names:

• chr16-56962051-C-A
• rs148628525
• NM_000078.3:c.72C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000078.3(CETP):​c.72C>A​(p.His24Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: CETP NM_000078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042067945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.72C>A	p.His24Gln	missense_variant	Exon 1 of 16	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.72C>A	p.His24Gln	missense_variant	Exon 1 of 15		NP_001273014.1
CETP	XM_006721124.4	c.72C>A	p.His24Gln	missense_variant	Exon 1 of 9		XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.72C>A	p.His24Gln	missense_variant	Exon 1 of 16	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.72C>A	p.His24Gln	missense_variant	Exon 1 of 15	1		ENSP00000369106.2
CETP	ENST00000569082.1	n.70C>A		non_coding_transcript_exon_variant	Exon 1 of 9	5
CETP	ENST00000566128.1	c.-323C>A		upstream_gene_variant		5		ENSP00000456276.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251066 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0060
DANN	Benign	0.67
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.48	N;N
REVEL	Benign	0.012
Sift	Benign	0.26	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.020	B;B
Vest4		0.050
MutPred		0.17		Loss of disorder (P = 0.1474);Loss of disorder (P = 0.1474);
MVP		0.11
MPC		0.13
ClinPred		0.031	T
GERP RS		-4.1
Varity_R		0.26
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs148628525; hg19: chr16-56995963;