20-45911925-C-T

Variant names:

• chr20-45911925-C-T
• rs2294212
• ENST00000477313.5:c.-473G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000477313.5(PLTP):​c.-473G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 85,418 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: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PLTP ENST00000477313.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 7 publications found

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

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=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLTP	NM_006227.4	c.-12+154G>A		intron_variant	Intron 1 of 15	ENST00000372431.8	NP_006218.1
PLTP	NM_182676.3	c.-12+154G>A		intron_variant	Intron 1 of 14		NP_872617.1
PLTP	NM_001242920.2	c.-12+154G>A		intron_variant	Intron 1 of 13		NP_001229849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000477313.5	c.-473G>A		5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000417138.1
PLTP	ENST00000372431.8	c.-12+154G>A		intron_variant	Intron 1 of 15	1	NM_006227.4	ENSP00000361508.3
PLTP	ENST00000354050.8	c.-12+154G>A		intron_variant	Intron 1 of 14	1		ENSP00000335290.4
PLTP	ENST00000420868.2	c.-12+154G>A		intron_variant	Intron 1 of 13	2		ENSP00000411671.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000117 AC: 1 AN: 85418 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 45736

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

African (AFR) AF: 0.00 AC: 0 AN: 2578

American (AMR) AF: 0.00 AC: 0 AN: 4016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1848

East Asian (EAS) AF: 0.000262 AC: 1 AN: 3820

South Asian (SAS) AF: 0.00 AC: 0 AN: 15358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 49578

Other (OTH) AF: 0.00 AC: 0 AN: 4168

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		0.21
PromoterAI		-0.0080	Neutral

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

Other links and lift over

dbSNP: rs2294212; hg19: chr20-44540564;