chr8-52642728-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014781.5(RB1CC1):ā€‹c.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

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.13
Variant links:
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]

Genome browser will be placed here

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
RB1CC1NM_014781.5 linkuse as main transcriptc.4072A>G p.Met1358Val missense_variant 17/24 ENST00000025008.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RB1CC1ENST00000025008.10 linkuse as main transcriptc.4072A>G p.Met1358Val missense_variant 17/241 NM_014781.5 P4Q8TDY2-1
RB1CC1ENST00000435644.6 linkuse as main transcriptc.4072A>G p.Met1358Val missense_variant 17/241 A1Q8TDY2-2
RB1CC1ENST00000522957.1 linkuse as main transcriptn.516A>G non_coding_transcript_exon_variant 1/83
RB1CC1ENST00000521611.1 linkuse as main transcriptn.386-19257A>G intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152228
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000687
AC:
15
AN:
218322
Hom.:
0
AF XY:
0.0000678
AC XY:
8
AN XY:
118012
show subpopulations
Gnomad AFR exome
AF:
0.000127
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000365
Gnomad SAS exome
AF:
0.000128
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000290
Gnomad OTH exome
AF:
0.000196
GnomAD4 exome
AF:
0.0000259
AC:
37
AN:
1428676
Hom.:
0
Cov.:
31
AF XY:
0.0000324
AC XY:
23
AN XY:
709870
show subpopulations
Gnomad4 AFR exome
AF:
0.0000635
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000177
Gnomad4 SAS exome
AF:
0.0000884
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000154
Gnomad4 OTH exome
AF:
0.0000509
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152228
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000330
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000742
AC:
9

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 submitterclinical testingAmbry GeneticsMar 16, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
21
DANN
Benign
0.76
DEOGEN2
Benign
0.22
T;.
Eigen
Benign
-0.17
Eigen_PC
Benign
0.017
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.079
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.81
L;L
MutationTaster
Benign
0.60
N;N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.23
N;N
REVEL
Benign
0.025
Sift
Benign
0.15
T;T
Sift4G
Benign
0.46
T;T
Polyphen
0.010
B;B
Vest4
0.33
MutPred
0.31
Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);
MVP
0.30
MPC
0.16
ClinPred
0.10
T
GERP RS
4.5
Varity_R
0.14
gMVP
0.30

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs751910131; hg19: chr8-53555288; API