Variant 8-52645747-A-T 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.3942T>A(p.Asn1314Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0088 in 1,612,838 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0062 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0091 ( 72 hom. )

Consequence

RB1CC1
NM_014781.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.357

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007832736).

BP6

Variant 8-52645747-A-T is Benign according to our data. Variant chr8-52645747-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 789296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 950 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RB1CC1	NM_014781.5 linkuse as main transcript	c.3942T>A	p.Asn1314Lys	missense_variant	16/24	ENST00000025008.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RB1CC1	ENST00000025008.10 linkuse as main transcript	c.3942T>A	p.Asn1314Lys	missense_variant	16/24	1	NM_014781.5	P4	Q8TDY2-1
RB1CC1	ENST00000435644.6 linkuse as main transcript	c.3942T>A	p.Asn1314Lys	missense_variant	16/24	1		A1	Q8TDY2-2
RB1CC1	ENST00000521611.1 linkuse as main transcript	n.386-22276T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00624

AC:

950

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.00396

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00672

AC:

1677

AN:

249598

Hom.:

AF XY:

0.00727

AC XY:

981

AN XY:

134878

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00296

Gnomad SAS exome

AF:

0.00842

Gnomad FIN exome

AF:

0.00421

Gnomad NFE exome

AF:

0.00959

Gnomad OTH exome

AF:

0.00805

GnomAD4 exome

AF:

0.00907

AC:

13250

AN:

1460550

Hom.:

Cov.:

AF XY:

0.00897

AC XY:

6514

AN XY:

726540

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00368

Gnomad4 ASJ exome

AF:

0.00264

Gnomad4 EAS exome

AF:

0.00415

Gnomad4 SAS exome

AF:

0.00858

Gnomad4 FIN exome

AF:

0.00465

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00802

GnomAD4 genome

AF:

0.00624

AC:

950

AN:

152288

Hom.:

Cov.:

AF XY:

0.00568

AC XY:

423

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00530

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00704

Gnomad4 FIN

AF:

0.00396

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00805

Hom.:

Bravo

AF:

0.00598

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0101

AC:

ExAC

AF:

0.00689

AC:

836

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00933

EpiControl

AF:

0.00902

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	RB1CC1: BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.97

D;D

MetaRNN

Benign

0.0078

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.15

Sift

Benign

0.067

T;T

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;D

Vest4

0.64

MutPred

0.097

Gain of ubiquitination at N1314 (P = 0.009);Gain of ubiquitination at N1314 (P = 0.009);

MVP

0.51

MPC

0.72

ClinPred

0.014

GERP RS

4.3

Varity_R

0.14

gMVP

0.42

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