9-110942155-T-C

Variant names:

• chr9-110942155-T-C
• rs757912248
• NM_001351411.2:c.59A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001351411.2(LPAR1):​c.59A>G​(p.Asn20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,609,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: LPAR1 NM_001351411.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.062420964).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351411.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPAR1	NM_001351411.2	MANE Select	c.59A>G	p.Asn20Ser	missense	Exon 5 of 6	NP_001338340.1	Q92633-1
	LPAR1	NM_001351397.2		c.59A>G	p.Asn20Ser	missense	Exon 4 of 5	NP_001338326.1	Q92633-1
	LPAR1	NM_001351398.2		c.59A>G	p.Asn20Ser	missense	Exon 6 of 7	NP_001338327.1	Q92633-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPAR1	ENST00000683809.1	MANE Select	c.59A>G	p.Asn20Ser	missense	Exon 5 of 6	ENSP00000506912.1	Q92633-1
	LPAR1	ENST00000374430.6	TSL:1	c.59A>G	p.Asn20Ser	missense	Exon 4 of 5	ENSP00000363552.1	Q92633-1
	LPAR1	ENST00000374431.7	TSL:1	c.59A>G	p.Asn20Ser	missense	Exon 4 of 5	ENSP00000363553.3	Q92633-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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

GnomAD2 exomes AF: 0.0000487 AC: 12 AN: 246564 AF XY: 0.0000451

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000657

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1457134 Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3 AN XY: 724506

African (AFR) AF: 0.00 AC: 0 AN: 33220

American (AMR) AF: 0.00 AC: 0 AN: 43760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25870

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39662

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 85022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110292

Other (OTH) AF: 0.00 AC: 0 AN: 60206

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.086
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.20	N
PhyloP100		3.1
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.23
Sift	Benign	0.20	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.050
MVP		0.78
MPC		0.59
ClinPred		0.065	T
GERP RS		3.1
Varity_R		0.038
gMVP		0.48
Mutation Taster		=95/5	polymorphism

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: rs757912248; hg19: chr9-113704435;