20-45902778-T-G

Variant names:

• chr20-45902778-T-G
• rs11569649
• NM_006227.4:c.943-174A>C

Variant summary

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

The NM_006227.4(PLTP):​c.943-174A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,304 control chromosomes in the GnomAD database, including 2,378 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 0.12 (2378 hom., cov: 33)
• Consequence: PLTP NM_006227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLTP	NM_006227.4	c.943-174A>C		intron_variant	Intron 10 of 15	ENST00000372431.8	NP_006218.1
PLTP	NM_182676.3	c.787-174A>C		intron_variant	Intron 9 of 14		NP_872617.1
PLTP	NM_001242921.1	c.679-174A>C		intron_variant	Intron 8 of 13		NP_001229850.1
PLTP	NM_001242920.2	c.658-174A>C		intron_variant	Intron 8 of 13		NP_001229849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8	c.943-174A>C		intron_variant	Intron 10 of 15	1	NM_006227.4	ENSP00000361508.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18077 AN: 152186 Hom.: 2367 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.00564

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.119 AC: 18121 AN: 152304 Hom.: 2378 Cov.: 33 AF XY: 0.118 AC XY: 8792 AN XY: 74486

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.0631

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.00564

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0611 Hom.: 209

Bravo AF: 0.131

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.80
DANN	Benign	0.47

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: rs11569649; hg19: chr20-44531417;