chr9-110941779-C-T

Variant names:

• chr9-110941779-C-T
• rs41279057
• NM_001351411.2:c.435G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001351411.2(LPAR1):​c.435G>A​(p.Glu145Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00408 in 1,614,202 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (24 hom.)
• Consequence: LPAR1 NM_001351411.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.65
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 9-110941779-C-T is Benign according to our data. Variant chr9-110941779-C-T is described in ClinVar as Benign. ClinVar VariationId is 770955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 406 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.435G>A	p.Glu145Glu	synonymous	Exon 5 of 6	NP_001338340.1	Q92633-1
	LPAR1	NM_001351397.2		c.435G>A	p.Glu145Glu	synonymous	Exon 4 of 5	NP_001338326.1	Q92633-1
	LPAR1	NM_001351398.2		c.435G>A	p.Glu145Glu	synonymous	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.435G>A	p.Glu145Glu	synonymous	Exon 5 of 6	ENSP00000506912.1	Q92633-1
	LPAR1	ENST00000374430.6	TSL:1	c.435G>A	p.Glu145Glu	synonymous	Exon 4 of 5	ENSP00000363552.1	Q92633-1
	LPAR1	ENST00000374431.7	TSL:1	c.435G>A	p.Glu145Glu	synonymous	Exon 4 of 5	ENSP00000363553.3	Q92633-1

Frequencies

GnomAD3 genomes AF: 0.00267 AC: 406 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00475

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00307 AC: 771 AN: 251022 AF XY: 0.00327

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.000597

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00482

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00423 AC: 6177 AN: 1461862 Hom.: 24 Cov.: 32 AF XY: 0.00419 AC XY: 3049 AN XY: 727232

African (AFR) AF: 0.00108 AC: 36 AN: 33480

American (AMR) AF: 0.00172 AC: 77 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000650 AC: 17 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00386 AC: 333 AN: 86258

European-Finnish (FIN) AF: 0.000505 AC: 27 AN: 53418

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5766

European-Non Finnish (NFE) AF: 0.00493 AC: 5485 AN: 1111992

Other (OTH) AF: 0.00323 AC: 195 AN: 60396

GnomAD4 genome AF: 0.00267 AC: 406 AN: 152340 Hom.: 0 Cov.: 32 AF XY: 0.00247 AC XY: 184 AN XY: 74484

African (AFR) AF: 0.000793 AC: 33 AN: 41590

American (AMR) AF: 0.00157 AC: 24 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4826

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00475 AC: 323 AN: 68032

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00402 Hom.: 1

Bravo AF: 0.00268

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00485

EpiControl AF: 0.00451

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		3.7
Mutation Taster		=100/0	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: rs41279057; hg19: chr9-113704059; COSMIC: COSV62687480;