rs3739709

chr9-110875574-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001351411.2(LPAR1):c.942C>T(p.Arg314=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,613,670 control chromosomes in the GnomAD database, including 27,371 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 0.15 (2010 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25361 hom.)
• Consequence: LPAR1 NM_001351411.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

Genes affected

LPAR1 (HGNC:3166): (lysophosphatidic acid receptor 1) The integral membrane protein encoded by this gene is a lysophosphatidic acid (LPA) receptor from a group known as EDG receptors. These receptors are members of the G protein-coupled receptor superfamily. Utilized by LPA for cell signaling, EDG receptors mediate diverse biologic functions, including proliferation, platelet aggregation, smooth muscle contraction, inhibition of neuroblastoma cell differentiation, chemotaxis, and tumor cell invasion. Many transcript variants encoding a few different isoforms have been identified for this gene. [provided by RefSeq, Oct 2020]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-1.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPAR1	NM_001351411.2	c.942C>T	p.Arg314=	synonymous_variant	6/6	ENST00000683809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPAR1	ENST00000683809.1	c.942C>T	p.Arg314=	synonymous_variant	6/6		NM_001351411.2	P1
LPAR1	ENST00000374430.6	c.942C>T	p.Arg314=	synonymous_variant	5/5	1		P1
LPAR1	ENST00000374431.7	c.942C>T	p.Arg314=	synonymous_variant	5/5	1		P1
LPAR1	ENST00000358883.8	c.942C>T	p.Arg314=	synonymous_variant	4/4	2		P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22302 AN: 151874 Hom.: 2011 Cov.: 32

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.177 AC: 44374 AN: 251160 Hom.: 4205 AF XY: 0.179 AC XY: 24250 AN XY: 135724

Gnomad AFR exome AF: 0.0396

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.182

Gnomad SAS exome AF: 0.170

Gnomad FIN exome AF: 0.176

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.183 AC: 267592 AN: 1461680 Hom.: 25361 Cov.: 34 AF XY: 0.184 AC XY: 133454 AN XY: 727140

Gnomad4 AFR exome AF: 0.0330

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.147 AC: 22294 AN: 151990 Hom.: 2010 Cov.: 32 AF XY: 0.149 AC XY: 11035 AN XY: 74258

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.142

Alfa AF: 0.181 Hom.: 6115

Bravo AF: 0.144

Asia WGS AF: 0.165 AC: 574 AN: 3478

EpiCase AF: 0.192

EpiControl AF: 0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	3.9
Dann	Benign	0.84

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: rs3739709; hg19: chr9-113637854; COSMIC: COSV62688259;