chr13-48412896-A-G

Variant names:

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

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.-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
• Publications: 28 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=-0.77).
• BP6: Variant 13-48412896-A-G is Benign according to our data. Variant chr13-48412896-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

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.-473T>C		5_prime_UTR	Exon 1 of 1	NP_001155970.1
	RB1	NM_000321.3	MANE Select	c.1695+31453A>G		intron	N/A	NP_000312.2
	LPAR6	NM_001162497.3		c.-473T>C		5_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.-473T>C		5_prime_UTR	Exon 1 of 1	ENSP00000482660.1
	LPAR6	ENST00000378434.8	TSL:1	c.-473T>C		5_prime_UTR	Exon 7 of 7	ENSP00000367691.3
	RB1	ENST00000267163.6	TSL:1 MANE Select	c.1695+31453A>G		intron	N/A	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

African (AFR) AF: 0.0147 AC: 1 AN: 68

American (AMR) AF: 0.156 AC: 188 AN: 1206

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 11 AN: 116

East Asian (EAS) AF: 0.0811 AC: 30 AN: 370

South Asian (SAS) AF: 0.117 AC: 162 AN: 1380

European-Finnish (FIN) AF: 0.124 AC: 1834 AN: 14800

Middle Eastern (MID) AF: 0.214 AC: 3 AN: 14

European-Non Finnish (NFE) AF: 0.122 AC: 729 AN: 5996

Other (OTH) AF: 0.110 AC: 54 AN: 490

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

African (AFR) AF: 0.0539 AC: 2242 AN: 41560

American (AMR) AF: 0.167 AC: 2556 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3472

East Asian (EAS) AF: 0.0868 AC: 450 AN: 5186

South Asian (SAS) AF: 0.118 AC: 571 AN: 4830

European-Finnish (FIN) AF: 0.128 AC: 1357 AN: 10610

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8882 AN: 68014

Other (OTH) AF: 0.111 AC: 235 AN: 2116

Alfa AF: 0.123 Hom.: 1885

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

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)

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		0.93
PromoterAI		0.063	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2227311; hg19: chr13-48987032;