20-45912053-C-G

Variant names:

• chr20-45912053-C-G
• rs2294213
• NM_006227.4:c.-12+26G>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15086 AN: 152090 Hom.: 934 Cov.: 33

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.: 64 Cov.: 0 AF XY: 0.0862 AC XY: 581 AN XY: 6742

Gnomad4 AFR exome AF: 0.0460

Gnomad4 AMR exome AF: 0.0498

Gnomad4 ASJ exome AF: 0.0472

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0503

Gnomad4 NFE exome AF: 0.0826

Gnomad4 OTH exome AF: 0.0606

GnomAD4 genome AF: 0.0991 AC: 15086 AN: 152208 Hom.: 937 Cov.: 33 AF XY: 0.101 AC XY: 7550 AN XY: 74420

Gnomad4 AFR AF: 0.0626

Gnomad4 AMR AF: 0.0611

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0398 Hom.: 46

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	11
DANN	Benign	0.65

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: rs2294213; hg19: chr20-44540692;