9-110942033-T-C

Variant summary

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

The NM_001351411.2(LPAR1):ā€‹c.181A>Gā€‹(p.Ile61Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00011 ( 0 hom., cov: 33)
Exomes š‘“: 0.00012 ( 0 hom. )

Consequence

LPAR1
NM_001351411.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40
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]

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=0.07022539).
BS2
High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LPAR1NM_001351411.2 linkc.181A>G p.Ile61Val missense_variant 5/6 ENST00000683809.1 NP_001338340.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LPAR1ENST00000683809.1 linkc.181A>G p.Ile61Val missense_variant 5/6 NM_001351411.2 ENSP00000506912.1 Q92633-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152136
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000916
AC:
23
AN:
251104
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135688
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000289
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:
0.000176
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000122
AC:
178
AN:
1461878
Hom.:
0
Cov.:
32
AF XY:
0.000125
AC XY:
91
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000144
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152136
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.0000966
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000198
Hom.:
0
Bravo
AF:
0.000166
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.000327
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsJan 03, 2024The c.181A>G (p.I61V) alteration is located in exon 4 (coding exon 2) of the LPAR1 gene. This alteration results from a A to G substitution at nucleotide position 181, causing the isoleucine (I) at amino acid position 61 to be replaced by a valine (V). 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
0.057
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
15
DANN
Benign
0.60
DEOGEN2
Benign
0.066
T;T;T;T;.
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.84
.;.;T;T;D
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.070
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.99
L;L;L;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
0.060
N;N;N;.;N
REVEL
Benign
0.048
Sift
Benign
0.93
T;T;T;.;T
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.0
B;B;B;.;.
Vest4
0.13
MVP
0.27
MPC
0.62
ClinPred
0.0072
T
GERP RS
4.2
Varity_R
0.047
gMVP
0.46

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.

Other links and lift over

dbSNP: rs147151638; hg19: chr9-113704313; API