20-45911925-C-G

Position:

• chr20-45911925-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000477313.5(PLTP):​c.-473G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 237,560 control chromosomes in the GnomAD database, including 1,646 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 0.099 (934 hom., cov: 33)
  • Exomes 𝑓: 0.11 (712 hom.)
• Consequence: PLTP ENST00000477313.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215

Genes affected

PLTP (HGNC:9093): (phospholipid transfer protein) The protein encoded by this gene is one of at least two lipid transfer proteins found in human plasma. The encoded protein transfers phospholipids from triglyceride-rich lipoproteins to high density lipoprotein (HDL). In addition to regulating the size of HDL particles, this protein may be involved in cholesterol metabolism. At least two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLTP	NM_006227.4	c.-12+154G>C		intron_variant		ENST00000372431.8	NP_006218.1
PLTP	NM_001242920.2	c.-12+154G>C		intron_variant			NP_001229849.1
PLTP	NM_182676.3	c.-12+154G>C		intron_variant			NP_872617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000477313.5	c.-473G>C		5_prime_UTR_variant	1/15	1		ENSP00000417138	P1
PLTP	ENST00000372431.8	c.-12+154G>C		intron_variant		1	NM_006227.4	ENSP00000361508	P1
PLTP	ENST00000354050.8	c.-12+154G>C		intron_variant		1		ENSP00000335290
PLTP	ENST00000420868.2	c.-12+154G>C		intron_variant		2		ENSP00000411671

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 15081 AN: 152136 Hom.: 931 Cov.: 33

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.0881

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0933

GnomAD4 exome AF: 0.107 AC: 9115 AN: 85306 Hom.: 712 Cov.: 0 AF XY: 0.110 AC XY: 5042 AN XY: 45680

Gnomad4 AFR exome AF: 0.0543

Gnomad4 AMR exome AF: 0.0588

Gnomad4 ASJ exome AF: 0.0795

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.0772

Gnomad4 NFE exome AF: 0.0928

Gnomad4 OTH exome AF: 0.0821

GnomAD4 genome AF: 0.0991 AC: 15081 AN: 152254 Hom.: 934 Cov.: 33 AF XY: 0.101 AC XY: 7551 AN XY: 74446

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.0610

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.0967 Hom.: 113

Bravo AF: 0.0938

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs2294212; hg19: chr20-44540564;