Variant X-78755611-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001278000.3(LPAR4):c.742C>G(p.Leu248Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,209,006 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

LPAR4
NM_001278000.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

LPAR4 (HGNC:4478): (lysophosphatidic acid receptor 4) This gene encodes a member of the lysophosphatidic acid receptor family. It may also be related to the P2Y receptors, a family of receptors that bind purine and pyrimidine nucleotides and are coupled to G proteins. The encoded protein may play a role in monocytic differentiation. [provided by RefSeq, Feb 2009]

LPAR4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34519792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPAR4	NM_001278000.3 linkuse as main transcript	c.742C>G	p.Leu248Val	missense_variant	5/5	ENST00000614823.5	NP_001264929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPAR4	ENST00000614823.5 linkuse as main transcript	c.742C>G	p.Leu248Val	missense_variant	5/5	4	NM_001278000.3	ENSP00000478261	P1
LPAR4	ENST00000435339.3 linkuse as main transcript	c.742C>G	p.Leu248Val	missense_variant	2/2	1		ENSP00000408205	P1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111577

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33829

show subpopulations

Gnomad AFR

AF:

0.0000977

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097429

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363023

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

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

AF:

0.0000269

AC:

AN:

111577

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33829

show subpopulations

Gnomad4 AFR

AF:

0.0000977

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.00000824

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

Jun 22, 2021

The c.742C>G (p.L248V) alteration is located in exon 2 (coding exon 1) of the LPAR4 gene. This alteration results from a C to G substitution at nucleotide position 742, causing the leucine (L) at amino acid position 248 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

0.15

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.069

T;T

FATHMM_MKL

Benign

0.66

LIST_S2

Pathogenic

0.97

D;.

M_CAP

Benign

0.036

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.84

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.1

.;N

REVEL

Uncertain

0.36

Sift

Benign

0.65

.;T

Sift4G

Benign

0.35

T;T

Polyphen

0.97

D;D

Vest4

0.44

MutPred

0.56

Gain of methylation at K249 (P = 0.0641);Gain of methylation at K249 (P = 0.0641);

MVP

0.40

MPC

1.1

ClinPred

0.74

GERP RS

0.25

Varity_R

0.14

gMVP

0.68

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