rs9866473

Variant names:

• chr3-171721908-G-A
• rs9866473
• NM_002662.5:c.758+2788C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

PLD1 Gene-Disease associations (from GenCC):

• cardiac valvular defect, developmental

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• PLD1-related congenital heart disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002662.5. 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
	PLD1	NM_002662.5	MANE Select	c.758+2788C>T		intron	N/A	NP_002653.1	Q13393-1
	PLD1	NM_001130081.3		c.758+2788C>T		intron	N/A	NP_001123553.1	Q13393-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD1	ENST00000351298.9	TSL:1 MANE Select	c.758+2788C>T		intron	N/A	ENSP00000342793.4	Q13393-1
	PLD1	ENST00000356327.9	TSL:1	c.758+2788C>T		intron	N/A	ENSP00000348681.5	Q13393-2
	PLD1	ENST00000959555.1		c.758+2788C>T		intron	N/A	ENSP00000629614.1

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

African (AFR) AF: 0.719 AC: 29798 AN: 41416

American (AMR) AF: 0.462 AC: 7060 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1188 AN: 3464

East Asian (EAS) AF: 0.329 AC: 1703 AN: 5172

South Asian (SAS) AF: 0.339 AC: 1628 AN: 4804

European-Finnish (FIN) AF: 0.562 AC: 5867 AN: 10444

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30482 AN: 67906

Other (OTH) AF: 0.459 AC: 970 AN: 2114

Alfa AF: 0.456 Hom.: 8493

Bravo AF: 0.523

Asia WGS AF: 0.359 AC: 1242 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.50
PhyloP100		-0.33
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: rs9866473; hg19: chr3-171439698;