rs6073952

Variant names:

• chr20-45908293-G-A
• rs6073952
• NM_006227.4:c.486-389C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006227.4(PLTP):​c.486-389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 151,994 control chromosomes in the GnomAD database, including 1,779 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 0.14 (1779 hom., cov: 31)
• Consequence: PLTP NM_006227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLTP	NM_006227.4	c.486-389C>T		intron_variant	Intron 5 of 15	ENST00000372431.8	NP_006218.1
PLTP	NM_182676.3	c.330-389C>T		intron_variant	Intron 4 of 14		NP_872617.1
PLTP	NM_001242921.1	c.222-389C>T		intron_variant	Intron 3 of 13		NP_001229850.1
PLTP	NM_001242920.2	c.201-389C>T		intron_variant	Intron 3 of 13		NP_001229849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8	c.486-389C>T		intron_variant	Intron 5 of 15	1	NM_006227.4	ENSP00000361508.3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21416 AN: 151876 Hom.: 1779 Cov.: 31

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.141 AC: 21421 AN: 151994 Hom.: 1779 Cov.: 31 AF XY: 0.141 AC XY: 10442 AN XY: 74290

African (AFR) AF: 0.0644 AC: 2671 AN: 41462

American (AMR) AF: 0.120 AC: 1829 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 664 AN: 3472

East Asian (EAS) AF: 0.0237 AC: 123 AN: 5180

South Asian (SAS) AF: 0.213 AC: 1024 AN: 4816

European-Finnish (FIN) AF: 0.145 AC: 1535 AN: 10554

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13053 AN: 67932

Other (OTH) AF: 0.147 AC: 311 AN: 2112

Alfa AF: 0.155 Hom.: 649

Bravo AF: 0.133

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.8
DANN	Benign	0.51
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6073952; hg19: chr20-44536932;