20-45909788-T-C

Variant names:

• chr20-45909788-T-C
• rs378114
• NM_006227.4:c.330-117A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006227.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLTP	NM_006227.4	MANE Select	c.330-117A>G		intron	N/A	NP_006218.1	P55058-1
	PLTP	NM_182676.3		c.329+154A>G		intron	N/A	NP_872617.1	P55058-2
	PLTP	NM_001242921.1		c.66-117A>G		intron	N/A	NP_001229850.1	P55058-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLTP	ENST00000372431.8	TSL:1 MANE Select	c.330-117A>G		intron	N/A	ENSP00000361508.3	P55058-1
	PLTP	ENST00000477313.5	TSL:1	c.330-117A>G		intron	N/A	ENSP00000417138.1	P55058-1
	PLTP	ENST00000354050.8	TSL:1	c.329+154A>G		intron	N/A	ENSP00000335290.4	P55058-2

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

African (AFR) AF: 0.619 AC: 18147 AN: 29332

American (AMR) AF: 0.862 AC: 36604 AN: 42466

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 15950 AN: 24524

East Asian (EAS) AF: 0.610 AC: 23385 AN: 38354

South Asian (SAS) AF: 0.696 AC: 56663 AN: 81384

European-Finnish (FIN) AF: 0.764 AC: 38189 AN: 49984

Middle Eastern (MID) AF: 0.690 AC: 3618 AN: 5246

European-Non Finnish (NFE) AF: 0.749 AC: 700786 AN: 935640

Other (OTH) AF: 0.729 AC: 38943 AN: 53386

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

African (AFR) AF: 0.621 AC: 25751 AN: 41460

American (AMR) AF: 0.814 AC: 12443 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2262 AN: 3472

East Asian (EAS) AF: 0.610 AC: 3155 AN: 5174

South Asian (SAS) AF: 0.694 AC: 3341 AN: 4812

European-Finnish (FIN) AF: 0.762 AC: 8064 AN: 10576

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50620 AN: 67986

Other (OTH) AF: 0.727 AC: 1535 AN: 2112

Alfa AF: 0.732 Hom.: 169190

Bravo AF: 0.710

Asia WGS AF: 0.698 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.62
PhyloP100		-1.5
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: rs378114; hg19: chr20-44538427;