20-45901995-A-G

Position:

• chr20-45901995-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006227.4(PLTP):​c.1175+272T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 152,222 control chromosomes in the GnomAD database, including 958 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 0.092 (958 hom., cov: 33)
• Consequence: PLTP NM_006227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLTP	NM_006227.4	c.1175+272T>C		intron_variant		ENST00000372431.8	NP_006218.1
PLTP	NM_182676.3	c.1019+272T>C		intron_variant			NP_872617.1
PLTP	NM_001242921.1	c.911+272T>C		intron_variant			NP_001229850.1
PLTP	NM_001242920.2	c.890+272T>C		intron_variant			NP_001229849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8	c.1175+272T>C		intron_variant		1	NM_006227.4	ENSP00000361508.3

Frequencies

GnomAD3 genomes AF: 0.0915 AC: 13924 AN: 152108 Hom.: 944 Cov.: 33

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.0917 AC: 13958 AN: 152222 Hom.: 958 Cov.: 33 AF XY: 0.0930 AC XY: 6924 AN XY: 74444

Gnomad4 AFR AF: 0.0781

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.0363

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0624

Gnomad4 NFE AF: 0.0678

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0832 Hom.: 1101

Bravo AF: 0.105

Asia WGS AF: 0.198 AC: 688 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	0.54
DANN	Benign	0.45

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

LitVar

Other links and lift over

dbSNP: rs1736493; hg19: chr20-44530634;