rs9568036

chr13-48397800-G-Achr13-48397800-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000321.3(RB1):c.1695+16357G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,916 control chromosomes in the GnomAD database, including 18,755 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (18755 hom., cov: 32)
• Consequence: RB1 NM_000321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RB1	NM_000321.3	c.1695+16357G>A		intron_variant		ENST00000267163.6
RB1	NM_001407165.1	c.1695+16357G>A		intron_variant
LPAR6	XM_047430023.1	c.193-6239C>T		intron_variant
LPAR6	XM_047430024.1	c.121-6239C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RB1	ENST00000267163.6	c.1695+16357G>A		intron_variant		1	NM_000321.3	P1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68149 AN: 151798 Hom.: 18755 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.492

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.449 AC: 68145 AN: 151916 Hom.: 18755 Cov.: 32 AF XY: 0.450 AC XY: 33387 AN XY: 74260

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.491

Alfa AF: 0.550 Hom.: 11038

Bravo AF: 0.428

Asia WGS AF: 0.486 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	17
Dann	Benign	0.57

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: rs9568036; hg19: chr13-48971936;