Variant chr15-89585735-C-T 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.1204C>T(p.Arg402Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 1,612,696 control chromosomes in the GnomAD database, including 195,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.44 ( 15341 hom., cov: 31)

Exomes 𝑓: 0.49 ( 180356 hom. )

Consequence

TICRR
NM_152259.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

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=1.6713142E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 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.1204C>T	p.Arg402Trp	missense_variant	4/22	ENST00000268138.12	NP_689472.3	Q7Z2Z1-1
TICRR	NM_001308025.1 linkuse as main transcript	c.1201C>T	p.Arg401Trp	missense_variant	4/22		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.1204C>T	p.Arg402Trp	missense_variant	4/22	5	NM_152259.4	ENSP00000268138.7	Q7Z2Z1-1
TICRR	ENST00000560985.5 linkuse as main transcript	c.1201C>T	p.Arg401Trp	missense_variant	4/22	1		ENSP00000453306.1	Q7Z2Z1-2
ENSG00000259713	ENST00000559041.1 linkuse as main transcript	n.48-5768C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

66995

AN:

151838

Hom.:

15342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.565

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.433

GnomAD3 exomes

AF:

0.453

AC:

112865

AN:

249114

Hom.:

26906

AF XY:

0.459

AC XY:

62075

AN XY:

135148

show subpopulations

Gnomad AFR exome

AF:

0.333

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.465

Gnomad EAS exome

AF:

0.233

Gnomad SAS exome

AF:

0.444

Gnomad FIN exome

AF:

0.561

Gnomad NFE exome

AF:

0.512

Gnomad OTH exome

AF:

0.460

GnomAD4 exome

AF:

0.492

AC:

719231

AN:

1460740

Hom.:

180356

Cov.:

AF XY:

0.491

AC XY:

357135

AN XY:

726740

show subpopulations

Gnomad4 AFR exome

AF:

0.326

Gnomad4 AMR exome

AF:

0.366

Gnomad4 ASJ exome

AF:

0.466

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.447

Gnomad4 FIN exome

AF:

0.553

Gnomad4 NFE exome

AF:

0.515

Gnomad4 OTH exome

AF:

0.468

GnomAD4 genome

AF:

0.441

AC:

67013

AN:

151956

Hom.:

15341

Cov.:

AF XY:

0.441

AC XY:

32770

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.395

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.425

Gnomad4 FIN

AF:

0.565

Gnomad4 NFE

AF:

0.512

Gnomad4 OTH

AF:

0.432

Alfa

AF:

0.490

Hom.:

31333

Bravo

AF:

0.422

TwinsUK

AF:

0.511

AC:

1896

ALSPAC

AF:

0.514

AC:

1982

ESP6500AA

AF:

0.333

AC:

1299

ESP6500EA

AF:

0.497

AC:

4109

ExAC

AF:

0.458

AC:

55308

Asia WGS

AF:

0.348

AC:

1211

AN:

3478

EpiCase

AF:

0.501

EpiControl

AF:

0.501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.033

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0019

T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.00017

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.5

N;.

PrimateAI

Benign

0.37

PROVEAN

Benign

4.0

N;N

REVEL

Benign

0.11

Sift

Benign

0.50

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0

B;.

Vest4

0.16

MPC

0.025

ClinPred

0.016

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.029

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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