9-110875574-G-A

Variant names:

• chr9-110875574-G-A
• rs3739709
• NM_001351411.2:c.942C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001351411.2(LPAR1):​c.942C>T​(p.Arg314Arg) 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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LPAR1	NM_001351411.2	c.942C>T	p.Arg314Arg	synonymous_variant	Exon 6 of 6	ENST00000683809.1	NP_001338340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAR1	ENST00000683809.1	c.942C>T	p.Arg314Arg	synonymous_variant	Exon 6 of 6		NM_001351411.2	ENSP00000506912.1
LPAR1	ENST00000374430.6	c.942C>T	p.Arg314Arg	synonymous_variant	Exon 5 of 5	1		ENSP00000363552.1
LPAR1	ENST00000374431.7	c.942C>T	p.Arg314Arg	synonymous_variant	Exon 5 of 5	1		ENSP00000363553.3
LPAR1	ENST00000358883.8	c.942C>T	p.Arg314Arg	synonymous_variant	Exon 4 of 4	2		ENSP00000351755.4

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

GnomAD2 exomes AF: 0.177 AC: 44374 AN: 251160 AF XY: 0.179

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 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

African (AFR) AF: 0.0330 AC: 1106 AN: 33480

American (AMR) AF: 0.198 AC: 8864 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 4100 AN: 26136

East Asian (EAS) AF: 0.184 AC: 7321 AN: 39696

South Asian (SAS) AF: 0.173 AC: 14885 AN: 86256

European-Finnish (FIN) AF: 0.185 AC: 9905 AN: 53420

Middle Eastern (MID) AF: 0.117 AC: 676 AN: 5764

European-Non Finnish (NFE) AF: 0.190 AC: 210743 AN: 1111816

Other (OTH) AF: 0.165 AC: 9992 AN: 60390

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

African (AFR) AF: 0.0398 AC: 1653 AN: 41500

American (AMR) AF: 0.201 AC: 3072 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3468

East Asian (EAS) AF: 0.175 AC: 903 AN: 5152

South Asian (SAS) AF: 0.169 AC: 815 AN: 4814

European-Finnish (FIN) AF: 0.173 AC: 1818 AN: 10536

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12994 AN: 67958

Other (OTH) AF: 0.142 AC: 299 AN: 2106

Alfa AF: 0.174 Hom.: 8129

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
PhyloP100		-1.5
Mutation Taster		=98/2	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: rs3739709; hg19: chr9-113637854; COSMIC: COSV62688259;