Genetic Variant LPAR5:p.Ala153Ala (chr12-6620790-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_020400.6(LPAR5):c.459C>T(p.Ala153Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,580,442 control chromosomes in the GnomAD database, including 350 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 0.013 ( 27 hom., cov: 32)

Exomes 𝑓: 0.019 ( 323 hom. )

Consequence

LPAR5
NM_020400.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.658

Publications

2 publications found

Variant links:

Genes affected

LPAR5 (HGNC:13307): (lysophosphatidic acid receptor 5) This gene encodes a member of the rhodopsin class of G protein-coupled transmembrane receptors. This protein transmits extracellular signals from lysophosphatidic acid to cells through heterotrimeric G proteins and mediates numerous cellular processes. Many G protein receptors serve as targets for pharmaceutical drugs. Transcript variants of this gene have been described.[provided by RefSeq, Dec 2008]

LPAR5 links:

ENSG00000301109 (HGNC:):

ENSG00000301109 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP7

Synonymous conserved (PhyloP=-0.658 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0133 (2020/152342) while in subpopulation EAS AF = 0.0216 (112/5182). AF 95% confidence interval is 0.0193. There are 27 homozygotes in GnomAd4. There are 930 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAR5	NM_020400.6 link	c.459C>T	p.Ala153Ala	synonymous_variant	Exon 2 of 2	ENST00000329858.9	NP_065133.1	Q9H1C0Q5KU18
LPAR5	NM_001142961.1 link	c.459C>T	p.Ala153Ala	synonymous_variant	Exon 2 of 2		NP_001136433.1	Q9H1C0Q5KU18
LOC105369631	XR_007063192.1 link	n.658+3001G>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAR5	ENST00000329858.9 link	c.459C>T	p.Ala153Ala	synonymous_variant	Exon 2 of 2	1	NM_020400.6	ENSP00000327875.4		Q9H1C0

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2022

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0216

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.0138

AC:

2567

AN:

185374

AF XY:

0.0135

show subpopulations

Gnomad AFR exome

AF:

0.00241

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.00286

Gnomad EAS exome

AF:

0.0250

Gnomad FIN exome

AF:

0.0139

Gnomad NFE exome

AF:

0.0206

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.0195

AC:

27842

AN:

1428100

Hom.:

323

Cov.:

AF XY:

0.0189

AC XY:

13411

AN XY:

707792

show subpopulations

African (AFR)

AF:

0.00256

AC:

AN:

32814

American (AMR)

AF:

0.00584

AC:

234

AN:

40040

Ashkenazi Jewish (ASJ)

AF:

0.00258

AC:

AN:

25208

East Asian (EAS)

AF:

0.0327

AC:

1261

AN:

38566

South Asian (SAS)

AF:

0.00483

AC:

399

AN:

82674

European-Finnish (FIN)

AF:

0.0148

AC:

712

AN:

48260

Middle Eastern (MID)

AF:

0.00335

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.0219

AC:

24026

AN:

1095890

Other (OTH)

AF:

0.0177

AC:

1042

AN:

58972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1770

3541

5311

7082

8852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

896

1792

2688

3584

4480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0133

AC:

2020

AN:

152342

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

930

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00356

AC:

148

AN:

41590

American (AMR)

AF:

0.0107

AC:

164

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.0216

AC:

112

AN:

5182

South Asian (SAS)

AF:

0.00414

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0155

AC:

165

AN:

10628

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0202

AC:

1375

AN:

68018

Other (OTH)

AF:

0.0137

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

100

200

301

401

501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0157

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.00636

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.8

(source)

DANN

Benign

0.95

PhyloP100

-0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over