9-110994184-T-C

Variant names:

• chr9-110994184-T-C
• rs10980684
• NM_001351411.2:c.-181-20626A>G

Variant summary

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

The NM_001351411.2(LPAR1):​c.-181-20626A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,980 control chromosomes in the GnomAD database, including 7,658 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 0.32 (7658 hom., cov: 32)
• Consequence: LPAR1 NM_001351411.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAR1	NM_001351411.2	c.-181-20626A>G		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.-181-20626A>G		intron_variant	Intron 2 of 5		NM_001351411.2	ENSP00000506912.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47969 AN: 151862 Hom.: 7655 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.316 AC: 48024 AN: 151980 Hom.: 7658 Cov.: 32 AF XY: 0.311 AC XY: 23098 AN XY: 74272

African (AFR) AF: 0.334 AC: 13840 AN: 41438

American (AMR) AF: 0.339 AC: 5182 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1117 AN: 5162

South Asian (SAS) AF: 0.213 AC: 1029 AN: 4820

European-Finnish (FIN) AF: 0.278 AC: 2939 AN: 10560

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21969 AN: 67950

Other (OTH) AF: 0.292 AC: 613 AN: 2102

Alfa AF: 0.332 Hom.: 1473

Bravo AF: 0.322

Asia WGS AF: 0.248 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		-0.16
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: rs10980684; hg19: chr9-113756464;