20-45901995-A-G

Variant names:

• chr20-45901995-A-G
• rs1736493
• NM_006227.4:c.1175+272T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006227.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLTP	NM_006227.4	MANE Select	c.1175+272T>C		intron	N/A	NP_006218.1	P55058-1
	PLTP	NM_182676.3		c.1019+272T>C		intron	N/A	NP_872617.1	P55058-2
	PLTP	NM_001242921.1		c.911+272T>C		intron	N/A	NP_001229850.1	P55058-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLTP	ENST00000372431.8	TSL:1 MANE Select	c.1175+272T>C		intron	N/A	ENSP00000361508.3	P55058-1
	PLTP	ENST00000477313.5	TSL:1	c.1175+272T>C		intron	N/A	ENSP00000417138.1	P55058-1
	PLTP	ENST00000354050.8	TSL:1	c.1019+272T>C		intron	N/A	ENSP00000335290.4	P55058-2

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

African (AFR) AF: 0.0781 AC: 3246 AN: 41548

American (AMR) AF: 0.199 AC: 3042 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3472

East Asian (EAS) AF: 0.262 AC: 1356 AN: 5178

South Asian (SAS) AF: 0.135 AC: 651 AN: 4822

European-Finnish (FIN) AF: 0.0624 AC: 661 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0678 AC: 4611 AN: 67998

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.0853 Hom.: 1432

Bravo AF: 0.105

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.54
DANN	Benign	0.45
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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: rs1736493; hg19: chr20-44530634;