Genetic Variant PLTP:c.-12+26G>C (chr20-45912053-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 NM_006227.4(PLTP):c.-12+26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 164,878 control chromosomes in the GnomAD database, including 1,001 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 ( 937 hom., cov: 33)

Exomes 𝑓: 0.086 ( 64 hom. )

Consequence

PLTP
NM_006227.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.129

Publications

14 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=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PLTP	NM_006227.4 link	c.-12+26G>C	intron_variant	Intron 1 of 15	ENST00000372431.8	NP_006218.1	P55058-1
PLTP	NM_182676.3 link	c.-12+26G>C	intron_variant	Intron 1 of 14		NP_872617.1	P55058-2
PLTP	NM_001242920.2 link	c.-12+26G>C	intron_variant	Intron 1 of 13		NP_001229849.1	P55058-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLTP	ENST00000372431.8 link	c.-12+26G>C	intron_variant	Intron 1 of 15	1	NM_006227.4	ENSP00000361508.3	P55058-1
PLTP	ENST00000354050.8 link	c.-12+26G>C	intron_variant	Intron 1 of 14	1		ENSP00000335290.4	P55058-2
PLTP	ENST00000420868.2 link	c.-12+26G>C	intron_variant	Intron 1 of 13	2		ENSP00000411671.2	P55058-3
PLTP	ENST00000477313.5 link	c.-601G>C	upstream_gene_variant		1		ENSP00000417138.1	P55058-1

Frequencies

GnomAD3 genomes

AF:

0.0992

AC:

15086

AN:

152090

Hom.:

934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0610

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0937

GnomAD4 exome

AF:

0.0857

AC:

1086

AN:

12670

Hom.:

Cov.:

AF XY:

0.0862

AC XY:

581

AN XY:

6742

show subpopulations

African (AFR)

AF:

0.0460

AC:

AN:

174

American (AMR)

AF:

0.0498

AC:

111

AN:

2228

Ashkenazi Jewish (ASJ)

AF:

0.0472

AC:

AN:

106

East Asian (EAS)

AF:

0.234

AC:

142

AN:

606

South Asian (SAS)

AF:

0.110

AC:

213

AN:

1932

European-Finnish (FIN)

AF:

0.0503

AC:

AN:

298

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0826

AC:

555

AN:

6718

Other (OTH)

AF:

0.0606

AC:

AN:

594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

128

171

214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

15086

AN:

152208

Hom.:

937

Cov.:

AF XY:

0.101

AC XY:

7550

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0626

AC:

2601

AN:

41530

American (AMR)

AF:

0.0611

AC:

935

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

370

AN:

3472

East Asian (EAS)

AF:

0.332

AC:

1710

AN:

5156

South Asian (SAS)

AF:

0.167

AC:

804

AN:

4820

European-Finnish (FIN)

AF:

0.106

AC:

1125

AN:

10612

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7235

AN:

68006

Other (OTH)

AF:

0.0918

AC:

194

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

690

1379

2069

2758

3448

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:

0.0398

Hom.:

Bravo

AF:

0.0939

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

-0.13

PromoterAI

0.072

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