Variant chr13-48411385-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001162498.3(LPAR6):c.*4A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000903 in 1,608,580 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 3 hom. )

Consequence

LPAR6
NM_001162498.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.19

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 13-48411385-T-C is Benign according to our data. Variant chr13-48411385-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1704919.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00473 (720/152362) while in subpopulation AFR AF= 0.0163 (677/41586). AF 95% confidence interval is 0.0153. There are 3 homozygotes in gnomad4. There are 327 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPAR6	NM_001162498.3 linkuse as main transcript	c.*4A>G		3_prime_UTR_variant	1/1	ENST00000620633.5
RB1	NM_000321.3 linkuse as main transcript	c.1695+29942T>C		intron_variant		ENST00000267163.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPAR6	ENST00000620633.5 linkuse as main transcript	c.*4A>G		3_prime_UTR_variant	1/1	5	NM_001162498.3	P1
RB1	ENST00000267163.6 linkuse as main transcript	c.1695+29942T>C		intron_variant		1	NM_000321.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00474

AC:

721

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00142

AC:

356

AN:

250314

Hom.:

AF XY:

0.00112

AC XY:

152

AN XY:

135300

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.000982

GnomAD4 exome

AF:

0.000503

AC:

732

AN:

1456218

Hom.:

Cov.:

AF XY:

0.000477

AC XY:

346

AN XY:

724664

show subpopulations

Gnomad4 AFR exome

AF:

0.0149

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000793

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.00473

AC:

720

AN:

152362

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

327

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0163

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00549

Asia WGS

AF:

0.00115

AC:

AN:

3476

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 07, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.82

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