Genetic Variant NM_006227.4:c.329+97C>A (chr20-45909845-G-T) – 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.329+97C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 1,519,400 control chromosomes in the GnomAD database, including 412,698 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 ( 38518 hom., cov: 32)

Exomes 𝑓: 0.74 ( 374180 hom. )

Consequence

PLTP
NM_006227.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.768

Publications

20 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:

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=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PLTP	NM_006227.4 link	c.329+97C>A	intron_variant	Intron 4 of 15	ENST00000372431.8	NP_006218.1	P55058-1
PLTP	NM_182676.3 link	c.329+97C>A	intron_variant	Intron 4 of 14		NP_872617.1	P55058-2
PLTP	NM_001242921.1 link	c.65+97C>A	intron_variant	Intron 2 of 13		NP_001229850.1	P55058-4
PLTP	NM_001242920.2 link	c.200+1307C>A	intron_variant	Intron 3 of 13		NP_001229849.1	P55058-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8 link	c.329+97C>A		intron_variant	Intron 4 of 15	1	NM_006227.4	ENSP00000361508.3		P55058-1

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107670

AN:

151898

Hom.:

38478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.620

Gnomad AMI

AF:

0.802

Gnomad AMR

AF:

0.812

Gnomad ASJ

AF:

0.642

Gnomad EAS

AF:

0.609

Gnomad SAS

AF:

0.690

Gnomad FIN

AF:

0.762

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.742

Gnomad OTH

AF:

0.724

GnomAD4 exome

AF:

0.738

AC:

1009389

AN:

1367384

Hom.:

374180

Cov.:

AF XY:

0.736

AC XY:

504251

AN XY:

685218

show subpopulations

African (AFR)

AF:

0.621

AC:

19451

AN:

31338

American (AMR)

AF:

0.861

AC:

37772

AN:

43864

Ashkenazi Jewish (ASJ)

AF:

0.641

AC:

16284

AN:

25394

East Asian (EAS)

AF:

0.609

AC:

23857

AN:

39184

South Asian (SAS)

AF:

0.694

AC:

58010

AN:

83552

European-Finnish (FIN)

AF:

0.764

AC:

39480

AN:

51648

Middle Eastern (MID)

AF:

0.691

AC:

3728

AN:

5396

European-Non Finnish (NFE)

AF:

0.747

AC:

769076

AN:

1029694

Other (OTH)

AF:

0.728

AC:

41731

AN:

57314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

14187

28375

42562

56750

70937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18224

36448

54672

72896

91120

<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:

0.709

AC:

107767

AN:

152016

Hom.:

38518

Cov.:

AF XY:

0.712

AC XY:

52875

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.620

AC:

25716

AN:

41450

American (AMR)

AF:

0.812

AC:

12404

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.642

AC:

2230

AN:

3472

East Asian (EAS)

AF:

0.608

AC:

3132

AN:

5148

South Asian (SAS)

AF:

0.691

AC:

3333

AN:

4822

European-Finnish (FIN)

AF:

0.762

AC:

8049

AN:

10564

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.742

AC:

50426

AN:

67968

Other (OTH)

AF:

0.726

AC:

1534

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1586

3171

4757

6342

7928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<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:

0.712

Hom.:

5865

Bravo

AF:

0.708

Asia WGS

AF:

0.697

AC:

2423

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.22

(source)

DANN

Benign

0.50

PhyloP100

-0.77

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