chr3-171753574-T-C

Variant names:

• chr3-171753574-T-C
• rs11708205
• NM_002662.5:c.-31-15492A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002662.5(PLD1):​c.-31-15492A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,144 control chromosomes in the GnomAD database, including 1,521 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 0.14 (1521 hom., cov: 32)
• Consequence: PLD1 NM_002662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 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.-31-15492A>G		intron	N/A	NP_002653.1	Q13393-1
	PLD1	NM_001130081.3		c.-31-15492A>G		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.-31-15492A>G		intron	N/A	ENSP00000342793.4	Q13393-1
	PLD1	ENST00000356327.9	TSL:1	c.-31-15492A>G		intron	N/A	ENSP00000348681.5	Q13393-2
	PLD1	ENST00000861048.1		c.-31-15492A>G		intron	N/A	ENSP00000531107.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21001 AN: 152026 Hom.: 1516 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.138 AC: 21016 AN: 152144 Hom.: 1521 Cov.: 32 AF XY: 0.140 AC XY: 10400 AN XY: 74390

African (AFR) AF: 0.124 AC: 5134 AN: 41522

American (AMR) AF: 0.105 AC: 1601 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 449 AN: 3466

East Asian (EAS) AF: 0.125 AC: 646 AN: 5150

South Asian (SAS) AF: 0.219 AC: 1054 AN: 4816

European-Finnish (FIN) AF: 0.140 AC: 1488 AN: 10604

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10067 AN: 67974

Other (OTH) AF: 0.150 AC: 317 AN: 2114

Alfa AF: 0.147 Hom.: 1259

Bravo AF: 0.133

Asia WGS AF: 0.158 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.47
PhyloP100		-1.1
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: rs11708205; hg19: chr3-171471364;