chr8-52642728-T-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_014781.5(RB1CC1):āc.4072A>Gā(p.Met1358Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000259 in 1,580,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000026 ( 0 hom. )
Consequence
RB1CC1
NM_014781.5 missense
NM_014781.5 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 5.13
Genes affected
RB1CC1 (HGNC:15574): (RB1 inducible coiled-coil 1) The protein encoded by this gene interacts with signaling pathways to coordinately regulate cell growth, cell proliferation, apoptosis, autophagy, and cell migration. This tumor suppressor also enhances retinoblastoma 1 gene expression in cancer cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.079046875).
BS2
High AC in GnomAdExome4 at 37 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1CC1 | NM_014781.5 | c.4072A>G | p.Met1358Val | missense_variant | 17/24 | ENST00000025008.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1CC1 | ENST00000025008.10 | c.4072A>G | p.Met1358Val | missense_variant | 17/24 | 1 | NM_014781.5 | P4 | |
RB1CC1 | ENST00000435644.6 | c.4072A>G | p.Met1358Val | missense_variant | 17/24 | 1 | A1 | ||
RB1CC1 | ENST00000522957.1 | n.516A>G | non_coding_transcript_exon_variant | 1/8 | 3 | ||||
RB1CC1 | ENST00000521611.1 | n.386-19257A>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152228Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000687 AC: 15AN: 218322Hom.: 0 AF XY: 0.0000678 AC XY: 8AN XY: 118012
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GnomAD4 exome AF: 0.0000259 AC: 37AN: 1428676Hom.: 0 Cov.: 31 AF XY: 0.0000324 AC XY: 23AN XY: 709870
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74370
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 16, 2024 | The c.4072A>G (p.M1358V) alteration is located in exon 17 (coding exon 15) of the RB1CC1 gene. This alteration results from a A to G substitution at nucleotide position 4072, causing the methionine (M) at amino acid position 1358 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at