20-45902199-G-T

Position:

• chr20-45902199-G-T

Variant summary

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

The NM_006227.4(PLTP):​c.1175+68C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,519,638 control chromosomes in the GnomAD database, including 315,946 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 0.65 (32317 hom., cov: 33)
  • Exomes 𝑓: 0.64 (283629 hom.)
• Consequence: PLTP NM_006227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLTP	NM_006227.4	c.1175+68C>A		intron_variant		ENST00000372431.8	NP_006218.1
PLTP	NM_182676.3	c.1019+68C>A		intron_variant			NP_872617.1
PLTP	NM_001242921.1	c.911+68C>A		intron_variant			NP_001229850.1
PLTP	NM_001242920.2	c.890+68C>A		intron_variant			NP_001229849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8	c.1175+68C>A		intron_variant		1	NM_006227.4	ENSP00000361508.3

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98975 AN: 152024 Hom.: 32266 Cov.: 33

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 0.643 AC: 878830 AN: 1367496 Hom.: 283629 AF XY: 0.642 AC XY: 438779 AN XY: 683216

Gnomad4 AFR exome AF: 0.651

Gnomad4 AMR exome AF: 0.772

Gnomad4 ASJ exome AF: 0.521

Gnomad4 EAS exome AF: 0.701

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.695

Gnomad4 NFE exome AF: 0.634

Gnomad4 OTH exome AF: 0.635

GnomAD4 genome AF: 0.651 AC: 99086 AN: 152142 Hom.: 32317 Cov.: 33 AF XY: 0.655 AC XY: 48714 AN XY: 74368

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.641

Alfa AF: 0.635 Hom.: 6656

Bravo AF: 0.650

Asia WGS AF: 0.711 AC: 2470 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.47

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: rs553359; hg19: chr20-44530838; COSMIC: COSV51944372; COSMIC: COSV51944372;