rs10817133

Variant names:

• chr9-111029694-A-G
• rs10817133
• NM_001351411.2:c.-182+6428T>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.-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
• 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]

ENSG00000301611 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351411.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPAR1	NM_001351411.2	MANE Select	c.-182+6428T>C		intron	N/A	NP_001338340.1
	LPAR1	NM_001351397.2		c.-182+9176T>C		intron	N/A	NP_001338326.1
	LPAR1	NM_001351398.2		c.-379+9176T>C		intron	N/A	NP_001338327.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPAR1	ENST00000683809.1	MANE Select	c.-182+6428T>C		intron	N/A	ENSP00000506912.1
	LPAR1	ENST00000374431.7	TSL:1	c.-182+8147T>C		intron	N/A	ENSP00000363553.3
	LPAR1	ENST00000358883.8	TSL:2	c.-104+8147T>C		intron	N/A	ENSP00000351755.4

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

African (AFR) AF: 0.244 AC: 10109 AN: 41362

American (AMR) AF: 0.320 AC: 4869 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3470

East Asian (EAS) AF: 0.610 AC: 3135 AN: 5138

South Asian (SAS) AF: 0.216 AC: 1040 AN: 4820

European-Finnish (FIN) AF: 0.220 AC: 2308 AN: 10510

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17426 AN: 67962

Other (OTH) AF: 0.291 AC: 615 AN: 2110

Alfa AF: 0.254 Hom.: 898

Bravo AF: 0.278

Asia WGS AF: 0.339 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.33
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10817133; hg19: chr9-113791974;