rs6065904

Variant names:

• chr20-45906012-G-A
• rs6065904
• NM_006227.4:c.705+256C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006227.4(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 NM_006227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 57 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLTP	NM_006227.4	MANE Select	c.705+256C>T		intron	N/A	NP_006218.1
	PLTP	NM_182676.3		c.549+256C>T		intron	N/A	NP_872617.1
	PLTP	NM_001242921.1		c.441+256C>T		intron	N/A	NP_001229850.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLTP	ENST00000372431.8	TSL:1 MANE Select	c.705+256C>T		intron	N/A	ENSP00000361508.3
	PLTP	ENST00000477313.5	TSL:1	c.705+256C>T		intron	N/A	ENSP00000417138.1
	PLTP	ENST00000354050.8	TSL:1	c.549+256C>T		intron	N/A	ENSP00000335290.4

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

African (AFR) AF: 0.223 AC: 9273 AN: 41508

American (AMR) AF: 0.311 AC: 4742 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 705 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1700 AN: 5182

South Asian (SAS) AF: 0.327 AC: 1580 AN: 4826

European-Finnish (FIN) AF: 0.233 AC: 2461 AN: 10572

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14845 AN: 67992

Other (OTH) AF: 0.233 AC: 492 AN: 2108

Alfa AF: 0.228 Hom.: 18944

Bravo AF: 0.244

Asia WGS AF: 0.383 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.5
DANN	Benign	0.46
PhyloP100		0.72
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: rs6065904; hg19: chr20-44534651;