20-45911539-A-G

Position:

• chr20-45911539-A-G

Variant summary

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

The ENST00000477313.5(PLTP):​c.-87T>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 0.556 in 1,577,670 control chromosomes in the GnomAD database, including 246,388 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 0.54 (22552 hom., cov: 33)
  • Exomes 𝑓: 0.56 (223836 hom.)
• Consequence: PLTP ENST00000477313.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLTP	NM_006227.4	c.-11-76T>C		intron_variant		ENST00000372431.8	NP_006218.1
PLTP	NM_182676.3	c.-11-76T>C		intron_variant			NP_872617.1
PLTP	NM_001242920.2	c.-11-76T>C		intron_variant			NP_001229849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000477313.5	c.-87T>C		5_prime_UTR_variant	1/15	1		ENSP00000417138.1
PLTP	ENST00000372431.8	c.-11-76T>C		intron_variant		1	NM_006227.4	ENSP00000361508.3
PLTP	ENST00000354050.8	c.-11-76T>C		intron_variant		1		ENSP00000335290.4
PLTP	ENST00000420868.2	c.-11-76T>C		intron_variant		2		ENSP00000411671.2

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82146 AN: 151940 Hom.: 22532 Cov.: 33

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.558

GnomAD3 exomes AF: 0.573 AC: 117734 AN: 205384 Hom.: 34544 AF XY: 0.563 AC XY: 64125 AN XY: 113976

Gnomad AFR exome AF: 0.454

Gnomad AMR exome AF: 0.767

Gnomad ASJ exome AF: 0.461

Gnomad EAS exome AF: 0.578

Gnomad SAS exome AF: 0.488

Gnomad FIN exome AF: 0.617

Gnomad NFE exome AF: 0.557

Gnomad OTH exome AF: 0.562

GnomAD4 exome AF: 0.557 AC: 794555 AN: 1425612 Hom.: 223836 Cov.: 30 AF XY: 0.554 AC XY: 392968 AN XY: 708988

Gnomad4 AFR exome AF: 0.449

Gnomad4 AMR exome AF: 0.754

Gnomad4 ASJ exome AF: 0.458

Gnomad4 EAS exome AF: 0.595

Gnomad4 SAS exome AF: 0.488

Gnomad4 FIN exome AF: 0.624

Gnomad4 NFE exome AF: 0.558

Gnomad4 OTH exome AF: 0.551

GnomAD4 genome AF: 0.541 AC: 82226 AN: 152058 Hom.: 22552 Cov.: 33 AF XY: 0.545 AC XY: 40548 AN XY: 74332

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.560

Alfa AF: 0.554 Hom.: 49683

Bravo AF: 0.543

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.43

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: rs394643; hg19: chr20-44540178; COSMIC: COSV62464205; COSMIC: COSV62464205;