rs9866473

Positions:

• chr3-171721908-G-A

Variant summary

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

The NM_002662.5(PLD1):​c.758+2788C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,792 control chromosomes in the GnomAD database, including 21,964 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 0.52 (21964 hom., cov: 31)
• Consequence: PLD1 NM_002662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

Genes affected

PLD1 (HGNC:9067): (phospholipase D1) This gene encodes a phosphatidylcholine-specific phospholipase which catalyzes the hydrolysis of phosphatidylcholine in order to yield phosphatidic acid and choline. The enzyme may play a role in signal transduction and subcellular trafficking. Alternative splicing results in multiple transcript variants with both catalytic and regulatory properties. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLD1	NM_002662.5	c.758+2788C>T		intron_variant		ENST00000351298.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD1	ENST00000351298.9	c.758+2788C>T		intron_variant		1	NM_002662.5	A1
PLD1	ENST00000356327.9	c.758+2788C>T		intron_variant		1		P4
PLD1	ENST00000475273.6	n.640-363C>T		intron_variant, non_coding_transcript_variant		5
PLD1	ENST00000498278.5	n.828+2788C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79126 AN: 151676 Hom.: 21917 Cov.: 31

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.522 AC: 79228 AN: 151792 Hom.: 21964 Cov.: 31 AF XY: 0.522 AC XY: 38712 AN XY: 74172

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.459

Alfa AF: 0.455 Hom.: 7555

Bravo AF: 0.523

Asia WGS AF: 0.359 AC: 1242 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.50

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: rs9866473; hg19: chr3-171439698;