13-48412896-A-G

Variant names:

• chr13-48412896-A-G
• rs2227311
• NM_001162498.3:c.-473T>C

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.-473T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 176,732 control chromosomes in the GnomAD database, including 1,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1040 hom., cov: 32)
  • Exomes 𝑓: 0.12 (191 hom.)
• Consequence: LPAR6 NM_001162498.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.933

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=-0.77).
• BP6: Variant 13-48412896-A-G is Benign according to our data. Variant chr13-48412896-A-G is described in ClinVar as [Benign]. Clinvar id is 1231305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAR6	NM_001162498.3	c.-473T>C		5_prime_UTR_variant	Exon 1 of 1	ENST00000620633.5	NP_001155970.1
RB1	NM_000321.3	c.1695+31453A>G		intron_variant	Intron 17 of 26	ENST00000267163.6	NP_000312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAR6	ENST00000620633.5	c.-473T>C		5_prime_UTR_variant	Exon 1 of 1	5	NM_001162498.3	ENSP00000482660.1
RB1	ENST00000267163.6	c.1695+31453A>G		intron_variant	Intron 17 of 26	1	NM_000321.3	ENSP00000267163.4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16784 AN: 152174 Hom.: 1042 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0868

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.123 AC: 3012 AN: 24440 Hom.: 191 Cov.: 0 AF XY: 0.123 AC XY: 1513 AN XY: 12324

Gnomad4 AFR exome AF: 0.0147

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.0948

Gnomad4 EAS exome AF: 0.0811

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.110 AC: 16781 AN: 152292 Hom.: 1040 Cov.: 32 AF XY: 0.112 AC XY: 8369 AN XY: 74462

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0868

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.111

Alfa AF: 0.126 Hom.: 1399

Bravo AF: 0.110

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 17047088) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2227311; hg19: chr13-48987032;