20-45909788-T-C

Position:

• chr20-45909788-T-C

Variant summary

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

The NM_006227.4(PLTP):​c.330-117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,412,392 control chromosomes in the GnomAD database, including 385,747 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 0.71 (38772 hom., cov: 31)
  • Exomes 𝑓: 0.74 (346975 hom.)
• Consequence: PLTP NM_006227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLTP	NM_006227.4	c.330-117A>G		intron_variant		ENST00000372431.8	NP_006218.1
PLTP	NM_182676.3	c.329+154A>G		intron_variant			NP_872617.1
PLTP	NM_001242921.1	c.66-117A>G		intron_variant			NP_001229850.1
PLTP	NM_001242920.2	c.200+1364A>G		intron_variant			NP_001229849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8	c.330-117A>G		intron_variant		1	NM_006227.4	ENSP00000361508.3

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108015 AN: 151958 Hom.: 38732 Cov.: 31

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.740 AC: 932285 AN: 1260316 Hom.: 346975 Cov.: 18 AF XY: 0.737 AC XY: 468145 AN XY: 634856

Gnomad4 AFR exome AF: 0.619

Gnomad4 AMR exome AF: 0.862

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.610

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.764

Gnomad4 NFE exome AF: 0.749

Gnomad4 OTH exome AF: 0.729

GnomAD4 genome AF: 0.711 AC: 108112 AN: 152076 Hom.: 38772 Cov.: 31 AF XY: 0.714 AC XY: 53030 AN XY: 74312

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.727

Alfa AF: 0.736 Hom.: 80799

Bravo AF: 0.710

Asia WGS AF: 0.698 AC: 2426 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	1.4
DANN	Benign	0.62

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: rs378114; hg19: chr20-44538427;