rs9568036

Variant names:

• chr13-48397800-G-A
• rs9568036
• NM_000321.3:c.1695+16357G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-48397800-G-A
• chr13-48397800-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

LPAR6 Gene-Disease associations (from GenCC):

• hypotrichosis 8

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• hypotrichosis simplex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated familial wooly hair disorder

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000321.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RB1	NM_000321.3	MANE Select	c.1695+16357G>A		intron	N/A	NP_000312.2	P06400
	RB1	NM_001407165.1		c.1695+16357G>A		intron	N/A	NP_001394094.1	A0A3B3IS71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RB1	ENST00000267163.6	TSL:1 MANE Select	c.1695+16357G>A		intron	N/A	ENSP00000267163.4	P06400
	LPAR6	ENST00000465365.6	TSL:1	n.1405+3498C>T		intron	N/A
	RB1	ENST00000467505.6	TSL:1	n.*1063+16357G>A		intron	N/A	ENSP00000434702.1	Q92728

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

African (AFR) AF: 0.108 AC: 4481 AN: 41402

American (AMR) AF: 0.519 AC: 7917 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2126 AN: 3470

East Asian (EAS) AF: 0.552 AC: 2857 AN: 5174

South Asian (SAS) AF: 0.527 AC: 2536 AN: 4812

European-Finnish (FIN) AF: 0.587 AC: 6189 AN: 10538

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40322 AN: 67946

Other (OTH) AF: 0.491 AC: 1037 AN: 2112

Alfa AF: 0.553 Hom.: 12399

Bravo AF: 0.428

Asia WGS AF: 0.486 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.57
PhyloP100		1.3
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: rs9568036; hg19: chr13-48971936;