20-45903841-C-T

Position:

• chr20-45903841-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006227.4(PLTP):​c.942+959G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 151,208 control chromosomes in the GnomAD database, including 40 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 0.021 (40 hom., cov: 33)
• Consequence: PLTP NM_006227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0212 (3213/151208) while in subpopulation NFE AF= 0.0303 (2053/67734). AF 95% confidence interval is 0.0292. There are 40 homozygotes in gnomad4. There are 1610 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLTP	NM_006227.4	c.942+959G>A		intron_variant		ENST00000372431.8	NP_006218.1
PLTP	NM_182676.3	c.786+959G>A		intron_variant			NP_872617.1
PLTP	NM_001242921.1	c.678+959G>A		intron_variant			NP_001229850.1
PLTP	NM_001242920.2	c.657+959G>A		intron_variant			NP_001229849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8	c.942+959G>A		intron_variant		1	NM_006227.4	ENSP00000361508.3

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3208 AN: 151088 Hom.: 40 Cov.: 33

Gnomad AFR AF: 0.00513

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.0256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0212 AC: 3213 AN: 151208 Hom.: 40 Cov.: 33 AF XY: 0.0218 AC XY: 1610 AN XY: 73828

Gnomad4 AFR AF: 0.00512

Gnomad4 AMR AF: 0.0275

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.000393

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0187

Gnomad4 NFE AF: 0.0303

Gnomad4 OTH AF: 0.0253

Alfa AF: 0.0129 Hom.: 14

Bravo AF: 0.0210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.98
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11569671; hg19: chr20-44532480;