Variant 9-110941433-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001351411.2(LPAR1):c.781G>A(p.Val261Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000686 in 1,458,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

LPAR1
NM_001351411.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

Variant links:

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]

LPAR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09909305).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPAR1	NM_001351411.2 linkuse as main transcript	c.781G>A	p.Val261Ile	missense_variant	5/6	ENST00000683809.1	NP_001338340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LPAR1	ENST00000683809.1 linkuse as main transcript	c.781G>A	p.Val261Ile	missense_variant	5/6		NM_001351411.2	ENSP00000506912.1	Q92633-1
LPAR1	ENST00000374430.6 linkuse as main transcript	c.781G>A	p.Val261Ile	missense_variant	4/5	1		ENSP00000363552.1	Q92633-1
LPAR1	ENST00000374431.7 linkuse as main transcript	c.781G>A	p.Val261Ile	missense_variant	4/5	1		ENSP00000363553.3	Q92633-1
LPAR1	ENST00000358883.8 linkuse as main transcript	c.781G>A	p.Val261Ile	missense_variant	3/4	2		ENSP00000351755.4	Q92633-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000403

AC:

AN:

248166

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134036

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1458188

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725010

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.781G>A (p.V261I) alteration is located in exon 4 (coding exon 2) of the LPAR1 gene. This alteration results from a G to A substitution at nucleotide position 781, causing the valine (V) at amino acid position 261 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.064

T;T;T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.077

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

.;.;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.099

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;L;L;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.23

N;N;N;.

REVEL

Benign

0.18

Sift

Benign

0.95

T;T;T;.

Sift4G

Benign

0.53

T;T;T;T

Polyphen

0.011

B;B;B;.

Vest4

0.37

MVP

0.15

MPC

0.77

ClinPred

0.071

GERP RS

5.2

Varity_R

0.11

gMVP

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over