rs7030789

Positions:

• chr9-110973232-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.-104+249T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,086 control chromosomes in the GnomAD database, including 35,126 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 0.68 (35126 hom., cov: 31)
• Consequence: LPAR1 NM_001351411.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPAR1	NM_001351411.2	c.-104+249T>C		intron_variant		ENST00000683809.1	NP_001338340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPAR1	ENST00000683809.1	c.-104+249T>C		intron_variant			NM_001351411.2	ENSP00000506912	P1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102800 AN: 151968 Hom.: 35087 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.677 AC: 102893 AN: 152086 Hom.: 35126 Cov.: 31 AF XY: 0.673 AC XY: 50010 AN XY: 74330

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.666

Alfa AF: 0.687 Hom.: 18458

Bravo AF: 0.676

Asia WGS AF: 0.510 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.60
DANN	Benign	0.43

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: rs7030789; hg19: chr9-113735512; COSMIC: COSV62687843;