chr13-48411303-G-T

Position:

• chr13-48411303-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001162498.3(LPAR6):​c.*86C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 1,087,814 control chromosomes in the GnomAD database, including 3,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (361 hom., cov: 32)
  • Exomes 𝑓: 0.075 (3079 hom.)
• Consequence: LPAR6 NM_001162498.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.128

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 13-48411303-G-T is Benign according to our data. Variant chr13-48411303-G-T is described in ClinVar as [Benign]. Clinvar id is 1234731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPAR6	NM_001162498.3	c.*86C>A		3_prime_UTR_variant	1/1	ENST00000620633.5
RB1	NM_000321.3	c.1695+29860G>T		intron_variant		ENST00000267163.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPAR6	ENST00000620633.5	c.*86C>A		3_prime_UTR_variant	1/1	5	NM_001162498.3	P1
RB1	ENST00000267163.6	c.1695+29860G>T		intron_variant		1	NM_000321.3	P1

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8861 AN: 152100 Hom.: 361 Cov.: 32

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.0777

GnomAD4 exome AF: 0.0753 AC: 70425 AN: 935596 Hom.: 3079 Cov.: 13 AF XY: 0.0740 AC XY: 36119 AN XY: 487826

Gnomad4 AFR exome AF: 0.0140

Gnomad4 AMR exome AF: 0.0443

Gnomad4 ASJ exome AF: 0.0895

Gnomad4 EAS exome AF: 0.000134

Gnomad4 SAS exome AF: 0.0173

Gnomad4 FIN exome AF: 0.0492

Gnomad4 NFE exome AF: 0.0924

Gnomad4 OTH exome AF: 0.0675

GnomAD4 genome AF: 0.0582 AC: 8853 AN: 152218 Hom.: 361 Cov.: 32 AF XY: 0.0539 AC XY: 4013 AN XY: 74422

Gnomad4 AFR AF: 0.0166

Gnomad4 AMR AF: 0.0552

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.0423

Gnomad4 NFE AF: 0.0913

Gnomad4 OTH AF: 0.0764

Alfa AF: 0.0780 Hom.: 152

Bravo AF: 0.0572

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs4151551; hg19: chr13-48985439;