20-45902778-T-G

Variant names:

• chr20-45902778-T-G
• rs11569649
• NM_006227.4:c.943-174A>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.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
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 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.943-174A>C		intron	N/A	NP_006218.1	P55058-1
	PLTP	NM_182676.3		c.787-174A>C		intron	N/A	NP_872617.1	P55058-2
	PLTP	NM_001242921.1		c.679-174A>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.943-174A>C		intron	N/A	ENSP00000361508.3	P55058-1
	PLTP	ENST00000477313.5	TSL:1	c.943-174A>C		intron	N/A	ENSP00000417138.1	P55058-1
	PLTP	ENST00000354050.8	TSL:1	c.787-174A>C		intron	N/A	ENSP00000335290.4	P55058-2

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

African (AFR) AF: 0.318 AC: 13198 AN: 41542

American (AMR) AF: 0.0631 AC: 966 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3470

East Asian (EAS) AF: 0.202 AC: 1049 AN: 5184

South Asian (SAS) AF: 0.144 AC: 694 AN: 4832

European-Finnish (FIN) AF: 0.00564 AC: 60 AN: 10630

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0210 AC: 1428 AN: 68028

Other (OTH) AF: 0.116 AC: 245 AN: 2114

Alfa AF: 0.0436 Hom.: 721

Bravo AF: 0.131

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.80
DANN	Benign	0.47
PhyloP100		-0.30
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: rs11569649; hg19: chr20-44531417;