dbSNP rs378114: PLTP:c.330-117A>T (chr20-45909788-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006227.4(PLTP):c.330-117A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000424 in 1,414,326 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

PLTP
NM_006227.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

28 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PLTP	NM_006227.4 link	c.330-117A>T	intron_variant	Intron 4 of 15	ENST00000372431.8	NP_006218.1	P55058-1
PLTP	NM_182676.3 link	c.329+154A>T	intron_variant	Intron 4 of 14		NP_872617.1	P55058-2
PLTP	NM_001242921.1 link	c.66-117A>T	intron_variant	Intron 2 of 13		NP_001229850.1	P55058-4
PLTP	NM_001242920.2 link	c.200+1364A>T	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.330-117A>T		intron_variant	Intron 4 of 15	1	NM_006227.4	ENSP00000361508.3		P55058-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000317

AC:

AN:

1262314

Hom.:

Cov.:

AF XY:

0.00000157

AC XY:

AN XY:

635788

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29374

American (AMR)

AF:

0.00

AC:

AN:

42484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24556

East Asian (EAS)

AF:

0.00

AC:

AN:

38368

South Asian (SAS)

AF:

0.00

AC:

AN:

81442

European-Finnish (FIN)

AF:

0.0000200

AC:

AN:

50024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5252

European-Non Finnish (NFE)

AF:

0.00000320

AC:

AN:

937350

Other (OTH)

AF:

0.00

AC:

AN:

53464

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0942227), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41360

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

169190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.3

(source)

DANN

Benign

0.76

PhyloP100

-1.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over