20-45902199-G-T

Variant summary

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

The NM_006227.4(PLTP):​c.1175+68C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,519,638 control chromosomes in the GnomAD database, including 315,946 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 0.65 ( 32317 hom., cov: 33)
Exomes 𝑓: 0.64 ( 283629 hom. )

Consequence

PLTP
NM_006227.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.618

Publications

15 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]

Genome browser will be placed here

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=-0.92).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLTPNM_006227.4 linkc.1175+68C>A intron_variant Intron 12 of 15 ENST00000372431.8 NP_006218.1 P55058-1
PLTPNM_182676.3 linkc.1019+68C>A intron_variant Intron 11 of 14 NP_872617.1 P55058-2
PLTPNM_001242921.1 linkc.911+68C>A intron_variant Intron 10 of 13 NP_001229850.1 P55058-4
PLTPNM_001242920.2 linkc.890+68C>A intron_variant Intron 10 of 13 NP_001229849.1 P55058-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLTPENST00000372431.8 linkc.1175+68C>A intron_variant Intron 12 of 15 1 NM_006227.4 ENSP00000361508.3 P55058-1

Frequencies

GnomAD3 genomes
AF:
0.651
AC:
98975
AN:
152024
Hom.:
32266
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.651
Gnomad AMI
AF:
0.593
Gnomad AMR
AF:
0.721
Gnomad ASJ
AF:
0.534
Gnomad EAS
AF:
0.687
Gnomad SAS
AF:
0.665
Gnomad FIN
AF:
0.707
Gnomad MID
AF:
0.589
Gnomad NFE
AF:
0.630
Gnomad OTH
AF:
0.638
GnomAD4 exome
AF:
0.643
AC:
878830
AN:
1367496
Hom.:
283629
AF XY:
0.642
AC XY:
438779
AN XY:
683216
show subpopulations
African (AFR)
AF:
0.651
AC:
20563
AN:
31576
American (AMR)
AF:
0.772
AC:
32027
AN:
41462
Ashkenazi Jewish (ASJ)
AF:
0.521
AC:
13131
AN:
25220
East Asian (EAS)
AF:
0.701
AC:
26879
AN:
38350
South Asian (SAS)
AF:
0.667
AC:
55133
AN:
82696
European-Finnish (FIN)
AF:
0.695
AC:
35843
AN:
51572
Middle Eastern (MID)
AF:
0.585
AC:
2599
AN:
4444
European-Non Finnish (NFE)
AF:
0.634
AC:
656354
AN:
1035022
Other (OTH)
AF:
0.635
AC:
36301
AN:
57154
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
17932
35863
53795
71726
89658
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
17100
34200
51300
68400
85500
<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:
0.651
AC:
99086
AN:
152142
Hom.:
32317
Cov.:
33
AF XY:
0.655
AC XY:
48714
AN XY:
74368
show subpopulations
African (AFR)
AF:
0.651
AC:
27033
AN:
41504
American (AMR)
AF:
0.721
AC:
11031
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.534
AC:
1853
AN:
3470
East Asian (EAS)
AF:
0.687
AC:
3545
AN:
5160
South Asian (SAS)
AF:
0.665
AC:
3211
AN:
4826
European-Finnish (FIN)
AF:
0.707
AC:
7474
AN:
10576
Middle Eastern (MID)
AF:
0.602
AC:
177
AN:
294
European-Non Finnish (NFE)
AF:
0.630
AC:
42865
AN:
67988
Other (OTH)
AF:
0.641
AC:
1356
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1800
3600
5401
7201
9001
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
808
1616
2424
3232
4040
<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:
0.637
Hom.:
11194
Bravo
AF:
0.650
Asia WGS
AF:
0.711
AC:
2470
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.11
DANN
Benign
0.47
PhyloP100
-0.62
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

Publications

Other links and lift over

dbSNP: rs553359; hg19: chr20-44530838; COSMIC: COSV51944372; COSMIC: COSV51944372; API