rs4366150

Variant names:

• chr9-110977358-A-G
• rs4366150
• NM_001351411.2:c.-181-3800T>C

Variant summary

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

The NM_001351411.2(LPAR1):​c.-181-3800T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,982 control chromosomes in the GnomAD database, including 9,452 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 0.33 (9452 hom., cov: 31)
• Consequence: LPAR1 NM_001351411.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAR1	NM_001351411.2	c.-181-3800T>C		intron_variant	Intron 2 of 5	ENST00000683809.1	NP_001338340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAR1	ENST00000683809.1	c.-181-3800T>C		intron_variant	Intron 2 of 5		NM_001351411.2	ENSP00000506912.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50711 AN: 151864 Hom.: 9450 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.334 AC: 50709 AN: 151982 Hom.: 9452 Cov.: 31 AF XY: 0.327 AC XY: 24260 AN XY: 74274

African (AFR) AF: 0.236 AC: 9769 AN: 41478

American (AMR) AF: 0.290 AC: 4425 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3470

East Asian (EAS) AF: 0.00252 AC: 13 AN: 5168

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4822

European-Finnish (FIN) AF: 0.362 AC: 3820 AN: 10546

Middle Eastern (MID) AF: 0.345 AC: 100 AN: 290

European-Non Finnish (NFE) AF: 0.425 AC: 28903 AN: 67930

Other (OTH) AF: 0.341 AC: 718 AN: 2106

Alfa AF: 0.395 Hom.: 7828

Bravo AF: 0.321

Asia WGS AF: 0.105 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		0.042
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: rs4366150; hg19: chr9-113739638;