chr20-45906012-G-A

Position:

• chr20-45906012-G-A

Variant summary

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

The ENST00000372431.8(PLTP):​c.705+256C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,124 control chromosomes in the GnomAD database, including 4,476 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 0.24 (4476 hom., cov: 32)
• Consequence: PLTP ENST00000372431.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLTP	NM_006227.4	c.705+256C>T		intron_variant		ENST00000372431.8	NP_006218.1
PLTP	NM_001242920.2	c.420+256C>T		intron_variant			NP_001229849.1
PLTP	NM_001242921.1	c.441+256C>T		intron_variant			NP_001229850.1
PLTP	NM_182676.3	c.549+256C>T		intron_variant			NP_872617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8	c.705+256C>T		intron_variant		1	NM_006227.4	ENSP00000361508	P1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35964 AN: 152004 Hom.: 4455 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.237 AC: 36025 AN: 152124 Hom.: 4476 Cov.: 32 AF XY: 0.242 AC XY: 17986 AN XY: 74392

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.233

Alfa AF: 0.224 Hom.: 8734

Bravo AF: 0.244

Asia WGS AF: 0.383 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.5
DANN	Benign	0.46

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: rs6065904; hg19: chr20-44534651;