Variant chr8-52636056-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014781.5(RB1CC1):c.4351A>G(p.Met1451Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00648 in 1,605,936 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 39 hom. )

Consequence

RB1CC1
NM_014781.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.50

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]

RB1CC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004251629).

BP6

Variant 8-52636056-T-C is Benign according to our data. Variant chr8-52636056-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 788734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 675 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RB1CC1	NM_014781.5 linkuse as main transcript	c.4351A>G	p.Met1451Val	missense_variant	19/24	ENST00000025008.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RB1CC1	ENST00000025008.10 linkuse as main transcript	c.4351A>G	p.Met1451Val	missense_variant	19/24	1	NM_014781.5	P4	Q8TDY2-1

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

674

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00738

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00403

AC:

981

AN:

243484

Hom.:

AF XY:

0.00390

AC XY:

515

AN XY:

131888

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00357

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000403

Gnomad NFE exome

AF:

0.00726

Gnomad OTH exome

AF:

0.00401

GnomAD4 exome

AF:

0.00670

AC:

9733

AN:

1453626

Hom.:

Cov.:

AF XY:

0.00657

AC XY:

4753

AN XY:

723170

show subpopulations

Gnomad4 AFR exome

AF:

0.00136

Gnomad4 AMR exome

AF:

0.00381

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.000863

Gnomad4 NFE exome

AF:

0.00830

Gnomad4 OTH exome

AF:

0.00436

GnomAD4 genome

AF:

0.00443

AC:

675

AN:

152310

Hom.:

Cov.:

AF XY:

0.00412

AC XY:

307

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00740

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00703

Hom.:

Bravo

AF:

0.00490

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00865

AC:

ExAC

AF:

0.00406

AC:

492

Asia WGS

AF:

0.000579

AC:

AN:

3466

EpiCase

AF:

0.00717

EpiControl

AF:

0.00701

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.30

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

0.74

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.017

Sift

Benign

0.22

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.0

B;B

Vest4

0.15

MVP

0.25

MPC

0.16

ClinPred

0.0071

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.51

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over