13-48411303-G-T

Variant names:

• chr13-48411303-G-T
• rs4151551
• NM_001162498.3:c.*86C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

RB1 Gene-Disease associations (from GenCC):

• hereditary retinoblastoma

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
• retinoblastoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• melanoma

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001162498.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPAR6	NM_001162498.3	MANE Select	c.*86C>A		3_prime_UTR	Exon 1 of 1	NP_001155970.1
	RB1	NM_000321.3	MANE Select	c.1695+29860G>T		intron	N/A	NP_000312.2
	LPAR6	NM_001162497.3		c.*86C>A		3_prime_UTR	Exon 5 of 5	NP_001155969.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPAR6	ENST00000620633.5	TSL:5 MANE Select	c.*86C>A		3_prime_UTR	Exon 1 of 1	ENSP00000482660.1
	LPAR6	ENST00000378434.8	TSL:1	c.*86C>A		3_prime_UTR	Exon 7 of 7	ENSP00000367691.3
	RB1	ENST00000267163.6	TSL:1 MANE Select	c.1695+29860G>T		intron	N/A	ENSP00000267163.4

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

African (AFR) AF: 0.0140 AC: 322 AN: 23010

American (AMR) AF: 0.0443 AC: 1880 AN: 42466

Ashkenazi Jewish (ASJ) AF: 0.0895 AC: 2028 AN: 22648

East Asian (EAS) AF: 0.000134 AC: 5 AN: 37196

South Asian (SAS) AF: 0.0173 AC: 1290 AN: 74488

European-Finnish (FIN) AF: 0.0492 AC: 2151 AN: 43742

Middle Eastern (MID) AF: 0.0521 AC: 162 AN: 3110

European-Non Finnish (NFE) AF: 0.0924 AC: 59684 AN: 645916

Other (OTH) AF: 0.0675 AC: 2903 AN: 43020

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

African (AFR) AF: 0.0166 AC: 688 AN: 41550

American (AMR) AF: 0.0552 AC: 844 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4824

European-Finnish (FIN) AF: 0.0423 AC: 448 AN: 10598

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0913 AC: 6208 AN: 67986

Other (OTH) AF: 0.0764 AC: 161 AN: 2108

Alfa AF: 0.0641 Hom.: 165

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs4151551; hg19: chr13-48985439;