20-45904471-A-T

Position:

• chr20-45904471-A-T

Variant summary

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

The NM_006227.4(PLTP):​c.942+329T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,876 control chromosomes in the GnomAD database, including 30,245 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 0.63 (30245 hom., cov: 32)
• Consequence: PLTP NM_006227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18

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=-1.06).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLTP	NM_006227.4	c.942+329T>A		intron_variant		ENST00000372431.8	NP_006218.1
PLTP	NM_001242920.2	c.657+329T>A		intron_variant			NP_001229849.1
PLTP	NM_001242921.1	c.678+329T>A		intron_variant			NP_001229850.1
PLTP	NM_182676.3	c.786+329T>A		intron_variant			NP_872617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8	c.942+329T>A		intron_variant		1	NM_006227.4	ENSP00000361508	P1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95513 AN: 151758 Hom.: 30216 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.639

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.629 AC: 95587 AN: 151876 Hom.: 30245 Cov.: 32 AF XY: 0.629 AC XY: 46689 AN XY: 74208

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.636

Alfa AF: 0.635 Hom.: 3612

Bravo AF: 0.638

Asia WGS AF: 0.598 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.10
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: rs6073950; hg19: chr20-44533110;