RB1 p.Ser180*

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_000321.3(RB1):c.539_540-521delCGTAAGTAGTTCACAGAATGTTATTTTTCACTTAAAAAAAAAGATTTTTATGGAATAATCTCAAACATCTTGATAGTTAGGGTTAGTTTGATCGATTATAGCAGGCTACTTCATAAATTAAGCCCATAGATTTAAGTCCTGTGTAGATTATTTATCTTCTCACAAAGAAAATAGTATAAAATACATGCCTTGTACTACAAAGAAGAACTAATAAGGTGGAATTGATTCAGGACAGCATATCACCAACTCTGAGAAAAATGCAACAAATGCAAATTCATTGACTAAATCTTTATTGAGGGTCTGTTACAGGCACTTTATTAACTAATAATCAGCATAATTTCTGTGTGAGAATAAATGTAAAAATCTGTATTAAAATTTCCAAATGATTATTTTAAATGTATAATGCATGCTCTAACAGTATGCCCATGTAGAGCTCCAGAGTTTTTTCTTGGAAACAGAATGAGTAGTACATGAGATTTTCTGCCTCATTGGAGTAGTATTGAAGATAATTAATATAAAGGGAAATTGTATATTTACTGATTAATTGATATCAATCTATTAATTCCAACAAGTinsGA(p.Ser180delins???) variant causes a splice donor, missense, splice region, intron change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S180L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

RB1
NM_000321.3 splice_donor, missense, splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.18

Publications

0 publications found

Variant links:

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]

RB1 Gene-Disease associations (from GenCC):

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

RB1 links:

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new If you want to explore the variant's impact on the transcript NM_000321.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.013993542 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RB1	NM_000321.3	MANE Select	c.539_540-521delCGTAAGTAGTTCACAGAATGTTATTTTTCACTTAAAAAAAAAGATTTTTATGGAATAATCTCAAACATCTTGATAGTTAGGGTTAGTTTGATCGATTATAGCAGGCTACTTCATAAATTAAGCCCATAGATTTAAGTCCTGTGTAGATTATTTATCTTCTCACAAAGAAAATAGTATAAAATACATGCCTTGTACTACAAAGAAGAACTAATAAGGTGGAATTGATTCAGGACAGCATATCACCAACTCTGAGAAAAATGCAACAAATGCAAATTCATTGACTAAATCTTTATTGAGGGTCTGTTACAGGCACTTTATTAACTAATAATCAGCATAATTTCTGTGTGAGAATAAATGTAAAAATCTGTATTAAAATTTCCAAATGATTATTTTAAATGTATAATGCATGCTCTAACAGTATGCCCATGTAGAGCTCCAGAGTTTTTTCTTGGAAACAGAATGAGTAGTACATGAGATTTTCTGCCTCATTGGAGTAGTATTGAAGATAATTAATATAAAGGGAAATTGTATATTTACTGATTAATTGATATCAATCTATTAATTCCAACAAGTinsGA	p.Ser180delins???	splice_donor missense splice_region intron	N/A	NP_000312.2	P06400
RB1	NM_001407165.1		c.539_540-521delCGTAAGTAGTTCACAGAATGTTATTTTTCACTTAAAAAAAAAGATTTTTATGGAATAATCTCAAACATCTTGATAGTTAGGGTTAGTTTGATCGATTATAGCAGGCTACTTCATAAATTAAGCCCATAGATTTAAGTCCTGTGTAGATTATTTATCTTCTCACAAAGAAAATAGTATAAAATACATGCCTTGTACTACAAAGAAGAACTAATAAGGTGGAATTGATTCAGGACAGCATATCACCAACTCTGAGAAAAATGCAACAAATGCAAATTCATTGACTAAATCTTTATTGAGGGTCTGTTACAGGCACTTTATTAACTAATAATCAGCATAATTTCTGTGTGAGAATAAATGTAAAAATCTGTATTAAAATTTCCAAATGATTATTTTAAATGTATAATGCATGCTCTAACAGTATGCCCATGTAGAGCTCCAGAGTTTTTTCTTGGAAACAGAATGAGTAGTACATGAGATTTTCTGCCTCATTGGAGTAGTATTGAAGATAATTAATATAAAGGGAAATTGTATATTTACTGATTAATTGATATCAATCTATTAATTCCAACAAGTinsGA	p.Ser180delins???	splice_donor missense splice_region intron	N/A	NP_001394094.1	A0A3B3IS71
RB1	NM_001407166.1		c.539_540-521delCGTAAGTAGTTCACAGAATGTTATTTTTCACTTAAAAAAAAAGATTTTTATGGAATAATCTCAAACATCTTGATAGTTAGGGTTAGTTTGATCGATTATAGCAGGCTACTTCATAAATTAAGCCCATAGATTTAAGTCCTGTGTAGATTATTTATCTTCTCACAAAGAAAATAGTATAAAATACATGCCTTGTACTACAAAGAAGAACTAATAAGGTGGAATTGATTCAGGACAGCATATCACCAACTCTGAGAAAAATGCAACAAATGCAAATTCATTGACTAAATCTTTATTGAGGGTCTGTTACAGGCACTTTATTAACTAATAATCAGCATAATTTCTGTGTGAGAATAAATGTAAAAATCTGTATTAAAATTTCCAAATGATTATTTTAAATGTATAATGCATGCTCTAACAGTATGCCCATGTAGAGCTCCAGAGTTTTTTCTTGGAAACAGAATGAGTAGTACATGAGATTTTCTGCCTCATTGGAGTAGTATTGAAGATAATTAATATAAAGGGAAATTGTATATTTACTGATTAATTGATATCAATCTATTAATTCCAACAAGTinsGA	p.Ser180delins???	splice_donor missense splice_region intron	N/A	NP_001394095.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RB1	ENST00000267163.6	TSL:1 MANE Select	c.539_540-521delCGTAAGTAGTTCACAGAATGTTATTTTTCACTTAAAAAAAAAGATTTTTATGGAATAATCTCAAACATCTTGATAGTTAGGGTTAGTTTGATCGATTATAGCAGGCTACTTCATAAATTAAGCCCATAGATTTAAGTCCTGTGTAGATTATTTATCTTCTCACAAAGAAAATAGTATAAAATACATGCCTTGTACTACAAAGAAGAACTAATAAGGTGGAATTGATTCAGGACAGCATATCACCAACTCTGAGAAAAATGCAACAAATGCAAATTCATTGACTAAATCTTTATTGAGGGTCTGTTACAGGCACTTTATTAACTAATAATCAGCATAATTTCTGTGTGAGAATAAATGTAAAAATCTGTATTAAAATTTCCAAATGATTATTTTAAATGTATAATGCATGCTCTAACAGTATGCCCATGTAGAGCTCCAGAGTTTTTTCTTGGAAACAGAATGAGTAGTACATGAGATTTTCTGCCTCATTGGAGTAGTATTGAAGATAATTAATATAAAGGGAAATTGTATATTTACTGATTAATTGATATCAATCTATTAATTCCAACAAGTinsGA	p.Ser180delins???	splice_donor missense splice_region intron	N/A	ENSP00000267163.4	P06400
RB1	ENST00000467505.6	TSL:1	n.138-12154_138-11582delCGTAAGTAGTTCACAGAATGTTATTTTTCACTTAAAAAAAAAGATTTTTATGGAATAATCTCAAACATCTTGATAGTTAGGGTTAGTTTGATCGATTATAGCAGGCTACTTCATAAATTAAGCCCATAGATTTAAGTCCTGTGTAGATTATTTATCTTCTCACAAAGAAAATAGTATAAAATACATGCCTTGTACTACAAAGAAGAACTAATAAGGTGGAATTGATTCAGGACAGCATATCACCAACTCTGAGAAAAATGCAACAAATGCAAATTCATTGACTAAATCTTTATTGAGGGTCTGTTACAGGCACTTTATTAACTAATAATCAGCATAATTTCTGTGTGAGAATAAATGTAAAAATCTGTATTAAAATTTCCAAATGATTATTTTAAATGTATAATGCATGCTCTAACAGTATGCCCATGTAGAGCTCCAGAGTTTTTTCTTGGAAACAGAATGAGTAGTACATGAGATTTTCTGCCTCATTGGAGTAGTATTGAAGATAATTAATATAAAGGGAAATTGTATATTTACTGATTAATTGATATCAATCTATTAATTCCAACAAGTinsGA		intron	N/A	ENSP00000434702.1	Q92728
RB1	ENST00000924352.1		c.539_540delCGTAAGTAGTTCACAGAATGTTATTTTTCACTTAAAAAAAAAGATTTTTATGGAATAATCTCAAACATCTTGATAGTTAGGGTTAGTTTGATCGATTATAGCAGGCTACTTCATAAATTAAGCCCATAGATTTAAGTCCTGTGTAGATTATTTATCTTCTCACAAAGAAAATAGTATAAAATACATGCCTTGTACTACAAAGAAGAACTAATAAGGTGGAATTGATTCAGGACAGCATATCACCAACTCTGAGAAAAATGCAACAAATGCAAATTCATTGACTAAATCTTTATTGAGGGTCTGTTACAGGCACTTTATTAACTAATAATCAGCATAATTTCTGTGTGAGAATAAATGTAAAAATCTGTATTAAAATTTCCAAATGATTATTTTAAATGTATAATGCATGCTCTAACAGTATGCCCATGTAGAGCTCCAGAGTTTTTTCTTGGAAACAGAATGAGTAGTACATGAGATTTTCTGCCTCATTGGAGTAGTATTGAAGATAATTAATATAAAGGGAAATTGTATATTTACTGATTAATTGATATCAATCTATTAATTCCAACAAGTinsGA	p.Ser180fs	frameshift missense	Exon 6 of 28	ENSP00000594411.1

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over