rs10817133

chr9-111029694-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351411.2(LPAR1):c.-182+6428T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,808 control chromosomes in the GnomAD database, including 5,878 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 0.27 (5878 hom., cov: 30)
• Consequence: LPAR1 NM_001351411.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPAR1	NM_001351411.2	c.-182+6428T>C		intron_variant		ENST00000683809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPAR1	ENST00000683809.1	c.-182+6428T>C		intron_variant			NM_001351411.2	P1
LPAR1	ENST00000374431.7	c.-182+8147T>C		intron_variant		1		P1
LPAR1	ENST00000358883.8	c.-104+8147T>C		intron_variant		2		P1
LPAR1	ENST00000441240.1	c.-182+8473T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40787 AN: 151688 Hom.: 5879 Cov.: 30

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.269 AC: 40798 AN: 151808 Hom.: 5878 Cov.: 30 AF XY: 0.269 AC XY: 19984 AN XY: 74168

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.291

Alfa AF: 0.254 Hom.: 868

Bravo AF: 0.278

Asia WGS AF: 0.339 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.1
Dann	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10817133; hg19: chr9-113791974;