9-110935275-G-T

Variant names:

• chr9-110935275-G-T
• rs4246884
• NM_001351411.2:c.793+6146C>A

Variant summary

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

The NM_001351411.2(LPAR1):​c.793+6146C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,832 control chromosomes in the GnomAD database, including 31,936 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 0.63 (31936 hom., cov: 30)
• Consequence: LPAR1 NM_001351411.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAR1	NM_001351411.2	c.793+6146C>A		intron_variant	Intron 5 of 5	ENST00000683809.1	NP_001338340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAR1	ENST00000683809.1	c.793+6146C>A		intron_variant	Intron 5 of 5		NM_001351411.2	ENSP00000506912.1
LPAR1	ENST00000374430.6	c.793+6146C>A		intron_variant	Intron 4 of 4	1		ENSP00000363552.1
LPAR1	ENST00000374431.7	c.793+6146C>A		intron_variant	Intron 4 of 4	1		ENSP00000363553.3
LPAR1	ENST00000358883.8	c.793+6146C>A		intron_variant	Intron 3 of 3	2		ENSP00000351755.4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96139 AN: 151710 Hom.: 31885 Cov.: 30

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.634 AC: 96250 AN: 151832 Hom.: 31936 Cov.: 30 AF XY: 0.638 AC XY: 47331 AN XY: 74204

African (AFR) AF: 0.785 AC: 32494 AN: 41406

American (AMR) AF: 0.668 AC: 10187 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1683 AN: 3470

East Asian (EAS) AF: 0.969 AC: 5000 AN: 5162

South Asian (SAS) AF: 0.741 AC: 3556 AN: 4802

European-Finnish (FIN) AF: 0.531 AC: 5601 AN: 10554

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35600 AN: 67884

Other (OTH) AF: 0.629 AC: 1323 AN: 2104

Alfa AF: 0.557 Hom.: 39356

Bravo AF: 0.657

Asia WGS AF: 0.846 AC: 2939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.8
DANN	Benign	0.82
PhyloP100		-0.86
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: rs4246884; hg19: chr9-113697555;