Genetic Variant PLTP:c.-473G>C (chr20-45911925-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000477313.5(PLTP):c.-473G>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 0.102 in 237,560 control chromosomes in the GnomAD database, including 1,646 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 0.099 ( 934 hom., cov: 33)

Exomes 𝑓: 0.11 ( 712 hom. )

Consequence

PLTP
ENST00000477313.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.215

Publications

7 publications found

Variant links:

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]

PLTP links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PLTP	NM_006227.4 link	c.-12+154G>C	intron_variant	Intron 1 of 15	ENST00000372431.8	NP_006218.1	P55058-1
PLTP	NM_182676.3 link	c.-12+154G>C	intron_variant	Intron 1 of 14		NP_872617.1	P55058-2
PLTP	NM_001242920.2 link	c.-12+154G>C	intron_variant	Intron 1 of 13		NP_001229849.1	P55058-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLTP	ENST00000477313.5 link	c.-473G>C	5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000417138.1	P55058-1
PLTP	ENST00000372431.8 link	c.-12+154G>C	intron_variant	Intron 1 of 15	1	NM_006227.4	ENSP00000361508.3	P55058-1
PLTP	ENST00000354050.8 link	c.-12+154G>C	intron_variant	Intron 1 of 14	1		ENSP00000335290.4	P55058-2
PLTP	ENST00000420868.2 link	c.-12+154G>C	intron_variant	Intron 1 of 13	2		ENSP00000411671.2	P55058-3

Frequencies

GnomAD3 genomes

AF:

0.0991

AC:

15081

AN:

152136

Hom.:

931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.0881

Gnomad AMR

AF:

0.0608

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0933

GnomAD4 exome

AF:

0.107

AC:

9115

AN:

85306

Hom.:

712

Cov.:

AF XY:

0.110

AC XY:

5042

AN XY:

45680

show subpopulations

African (AFR)

AF:

0.0543

AC:

140

AN:

2578

American (AMR)

AF:

0.0588

AC:

236

AN:

4016

Ashkenazi Jewish (ASJ)

AF:

0.0795

AC:

147

AN:

1848

East Asian (EAS)

AF:

0.321

AC:

1221

AN:

3802

South Asian (SAS)

AF:

0.139

AC:

2128

AN:

15330

European-Finnish (FIN)

AF:

0.0772

AC:

292

AN:

3782

Middle Eastern (MID)

AF:

0.0593

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.0928

AC:

4593

AN:

49514

Other (OTH)

AF:

0.0821

AC:

342

AN:

4166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

386

772

1157

1543

1929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0991

AC:

15081

AN:

152254

Hom.:

934

Cov.:

AF XY:

0.101

AC XY:

7551

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0627

AC:

2605

AN:

41560

American (AMR)

AF:

0.0610

AC:

933

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

370

AN:

3470

East Asian (EAS)

AF:

0.331

AC:

1710

AN:

5160

South Asian (SAS)

AF:

0.166

AC:

803

AN:

4824

European-Finnish (FIN)

AF:

0.106

AC:

1123

AN:

10612

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7232

AN:

68018

Other (OTH)

AF:

0.0914

AC:

193

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

679

1357

2036

2714

3393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0967

Hom.:

113

Bravo

AF:

0.0938

Asia WGS

AF:

0.191

AC:

665

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.21

PromoterAI

0.013

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over