Variant chr13-48411623-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001162498.3(LPAR6):c.801A>C(p.Ala267=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,612,216 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 2 hom. )

Consequence

LPAR6
NM_001162498.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.83

Variant links:

Genes affected

LPAR6 (HGNC:15520): (lysophosphatidic acid receptor 6) The protein encoded by this gene belongs to the family of G-protein coupled receptors, that are preferentially activated by adenosine and uridine nucleotides. This gene aligns with an internal intron of the retinoblastoma susceptibility gene in the reverse orientation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2009]

LPAR6 links:

RB1 (HGNC:9884): (RB transcriptional corepressor 1) The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008]

RB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 13-48411623-T-G is Benign according to our data. Variant chr13-48411623-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 780057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.84 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00141 (214/152294) while in subpopulation NFE AF= 0.00251 (171/68008). AF 95% confidence interval is 0.00221. There are 1 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPAR6	NM_001162498.3 linkuse as main transcript	c.801A>C	p.Ala267=	synonymous_variant	1/1	ENST00000620633.5
RB1	NM_000321.3 linkuse as main transcript	c.1695+30180T>G		intron_variant		ENST00000267163.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPAR6	ENST00000620633.5 linkuse as main transcript	c.801A>C	p.Ala267=	synonymous_variant	1/1	5	NM_001162498.3	P1
RB1	ENST00000267163.6 linkuse as main transcript	c.1695+30180T>G		intron_variant		1	NM_000321.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

213

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00250

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00138

AC:

344

AN:

250116

Hom.:

AF XY:

0.00149

AC XY:

201

AN XY:

135282

show subpopulations

Gnomad AFR exome

AF:

0.000558

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00238

Gnomad OTH exome

AF:

0.000984

GnomAD4 exome

AF:

0.00250

AC:

3647

AN:

1459922

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

1799

AN XY:

726396

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000986

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00305

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00141

AC:

214

AN:

152294

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00251

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00136

EpiCase

AF:

0.00256

EpiControl

AF:

0.00202

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 27, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	LPAR6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.5

DANN

Benign

0.75

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