rs4490097

Positions:

• chr19-40355817-A-C
• chr19-40355817-A-T

Variant summary

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

The NM_012268.4(PLD3):​c.-279+7049A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,784 control chromosomes in the GnomAD database, including 12,131 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 0.37 (12126 hom., cov: 29)
  • Exomes 𝑓: 0.58 (5 hom.)
• Consequence: PLD3 NM_012268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

Genes affected

PLD3 (HGNC:17158): (phospholipase D family member 3) This gene encodes a member of the phospholipase D (PLD) family of enzymes that catalyze the hydrolysis of membrane phospholipids. The encoded protein is a single-pass type II membrane protein and contains two PLD phosphodiesterase domains. This protein influences processing of amyloid-beta precursor protein. Mutations in this gene are associated with Alzheimer disease risk. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Apr 2014]

(HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD3	NM_012268.4	c.-279+7049A>C		intron_variant		ENST00000409735.9	NP_036400.2
PLD3	NM_001031696.4	c.-99+7093A>C		intron_variant			NP_001026866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD3	ENST00000409735.9	c.-279+7049A>C		intron_variant		1	NM_012268.4	ENSP00000386938	P1
	ENST00000622968.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56655 AN: 151640 Hom.: 12129 Cov.: 29

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.577 AC: 15 AN: 26 Hom.: 5 Cov.: 0 AF XY: 0.545 AC XY: 12 AN XY: 22

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.611

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.373 AC: 56661 AN: 151758 Hom.: 12126 Cov.: 29 AF XY: 0.375 AC XY: 27805 AN XY: 74114

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.396

Alfa AF: 0.424 Hom.: 14023

Bravo AF: 0.371

Asia WGS AF: 0.529 AC: 1837 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.70

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: rs4490097; hg19: chr19-40861724; COSMIC: COSV62924932; COSMIC: COSV62924932;