Variant rs10775247 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152259.4(TICRR):c.859C>T(p.Arg287Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,613,896 control chromosomes in the GnomAD database, including 248,398 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.47 ( 18382 hom., cov: 33)

Exomes 𝑓: 0.56 ( 230016 hom. )

Consequence

TICRR
NM_152259.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.436

Variant links:

Genes affected

TICRR (HGNC:28704): (TOPBP1 interacting checkpoint and replication regulator) Enables chromatin binding activity. Involved in regulation of DNA-dependent DNA replication initiation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TICRR links:

ENSG00000259713 (HGNC:):

ENSG00000259713 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.037585E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TICRR	NM_152259.4 linkuse as main transcript	c.859C>T	p.Arg287Cys	missense_variant	2/22	ENST00000268138.12	NP_689472.3	Q7Z2Z1-1
TICRR	NM_001308025.1 linkuse as main transcript	c.859C>T	p.Arg287Cys	missense_variant	2/22		NP_001294954.1	Q7Z2Z1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TICRR	ENST00000268138.12 linkuse as main transcript	c.859C>T	p.Arg287Cys	missense_variant	2/22	5	NM_152259.4	ENSP00000268138.7	Q7Z2Z1-1
TICRR	ENST00000560985.5 linkuse as main transcript	c.859C>T	p.Arg287Cys	missense_variant	2/22	1		ENSP00000453306.1	Q7Z2Z1-2
ENSG00000259713	ENST00000559041.1 linkuse as main transcript	n.48-8613C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72124

AN:

151954

Hom.:

18382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.289

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.479

GnomAD3 exomes

AF:

0.507

AC:

126547

AN:

249522

Hom.:

33782

AF XY:

0.514

AC XY:

69645

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.288

Gnomad AMR exome

AF:

0.406

Gnomad ASJ exome

AF:

0.537

Gnomad EAS exome

AF:

0.319

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.612

Gnomad NFE exome

AF:

0.583

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.556

AC:

812058

AN:

1461824

Hom.:

230016

Cov.:

AF XY:

0.554

AC XY:

403207

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.277

Gnomad4 AMR exome

AF:

0.409

Gnomad4 ASJ exome

AF:

0.539

Gnomad4 EAS exome

AF:

0.306

Gnomad4 SAS exome

AF:

0.482

Gnomad4 FIN exome

AF:

0.611

Gnomad4 NFE exome

AF:

0.584

Gnomad4 OTH exome

AF:

0.522

GnomAD4 genome

AF:

0.474

AC:

72134

AN:

152072

Hom.:

18382

Cov.:

AF XY:

0.473

AC XY:

35200

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.288

Gnomad4 AMR

AF:

0.438

Gnomad4 ASJ

AF:

0.531

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.457

Gnomad4 FIN

AF:

0.615

Gnomad4 NFE

AF:

0.582

Gnomad4 OTH

AF:

0.478

Alfa

AF:

0.551

Hom.:

58399

Bravo

AF:

0.451

TwinsUK

AF:

0.584

AC:

2166

ALSPAC

AF:

0.580

AC:

2235

ESP6500AA

AF:

0.294

AC:

1139

ESP6500EA

AF:

0.567

AC:

4696

ExAC

AF:

0.511

AC:

61822

Asia WGS

AF:

0.388

AC:

1350

AN:

3478

EpiCase

AF:

0.567

EpiControl

AF:

0.564

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.3

DANN

Benign

0.82

DEOGEN2

Benign

0.0023

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0000090

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

3.8

N;N

REVEL

Benign

0.019

Sift

Benign

0.51

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0040

B;.

Vest4

0.059

MPC

0.029

ClinPred

0.0015

GERP RS

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.032

gMVP

0.34

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over