chr20-45911539-A-G

Variant names:

• chr20-45911539-A-G
• rs394643
• ENST00000477313.5:c.-87T>C

Variant summary

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

The ENST00000477313.5(PLTP):​c.-87T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,577,670 control chromosomes in the GnomAD database, including 246,388 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 0.54 (22552 hom., cov: 33)
  • Exomes 𝑓: 0.56 (223836 hom.)
• Consequence: PLTP ENST00000477313.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000477313.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLTP	NM_006227.4	MANE Select	c.-11-76T>C		intron	N/A	NP_006218.1
	PLTP	NM_182676.3		c.-11-76T>C		intron	N/A	NP_872617.1
	PLTP	NM_001242920.2		c.-11-76T>C		intron	N/A	NP_001229849.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLTP	ENST00000477313.5	TSL:1	c.-87T>C		5_prime_UTR	Exon 1 of 15	ENSP00000417138.1
	PLTP	ENST00000372431.8	TSL:1 MANE Select	c.-11-76T>C		intron	N/A	ENSP00000361508.3
	PLTP	ENST00000354050.8	TSL:1	c.-11-76T>C		intron	N/A	ENSP00000335290.4

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82146 AN: 151940 Hom.: 22532 Cov.: 33

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.558

GnomAD2 exomes AF: 0.573 AC: 117734 AN: 205384 AF XY: 0.563

Gnomad AFR exome AF: 0.454

Gnomad AMR exome AF: 0.767

Gnomad ASJ exome AF: 0.461

Gnomad EAS exome AF: 0.578

Gnomad FIN exome AF: 0.617

Gnomad NFE exome AF: 0.557

Gnomad OTH exome AF: 0.562

GnomAD4 exome AF: 0.557 AC: 794555 AN: 1425612 Hom.: 223836 Cov.: 30 AF XY: 0.554 AC XY: 392968 AN XY: 708988

African (AFR) AF: 0.449 AC: 14810 AN: 32952

American (AMR) AF: 0.754 AC: 31446 AN: 41692

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 11827 AN: 25804

East Asian (EAS) AF: 0.595 AC: 23154 AN: 38936

South Asian (SAS) AF: 0.488 AC: 41359 AN: 84774

European-Finnish (FIN) AF: 0.624 AC: 23346 AN: 37412

Middle Eastern (MID) AF: 0.552 AC: 3164 AN: 5728

European-Non Finnish (NFE) AF: 0.558 AC: 612661 AN: 1098808

Other (OTH) AF: 0.551 AC: 32788 AN: 59506

GnomAD4 genome AF: 0.541 AC: 82226 AN: 152058 Hom.: 22552 Cov.: 33 AF XY: 0.545 AC XY: 40548 AN XY: 74332

African (AFR) AF: 0.455 AC: 18884 AN: 41466

American (AMR) AF: 0.679 AC: 10383 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1596 AN: 3470

East Asian (EAS) AF: 0.586 AC: 3029 AN: 5166

South Asian (SAS) AF: 0.480 AC: 2313 AN: 4822

European-Finnish (FIN) AF: 0.620 AC: 6569 AN: 10588

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37545 AN: 67946

Other (OTH) AF: 0.560 AC: 1182 AN: 2110

Alfa AF: 0.551 Hom.: 102302

Bravo AF: 0.543

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.43
PhyloP100		-0.86
Mutation Taster		=300/0	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: rs394643; hg19: chr20-44540178; COSMIC: COSV62464205; COSMIC: COSV62464205;