Variant chr11-125625863-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000427383.6(CHEK1):c.103C>T(p.Arg35Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 702,640 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00084 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

CHEK1
ENST00000427383.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -9.83

Variant links:

Genes affected

CHEK1 (HGNC:1925): (checkpoint kinase 1) The protein encoded by this gene belongs to the Ser/Thr protein kinase family. It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2011]

CHEK1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039245784).

BP6

Variant 11-125625863-C-T is Benign according to our data. Variant chr11-125625863-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3050406.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 128 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHEK1	NM_001114122.3 linkuse as main transcript	c.-170C>T		5_prime_UTR_variant	1/13	ENST00000438015.7
LOC118567325	NR_170378.1 linkuse as main transcript	n.32G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHEK1	ENST00000438015.7 linkuse as main transcript	c.-170C>T		5_prime_UTR_variant	1/13	5	NM_001114122.3	P1	O14757-1
	ENST00000686400.2 linkuse as main transcript	n.51G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000841

AC:

128

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000999

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00123

AC:

160

AN:

130584

Hom.:

AF XY:

0.00147

AC XY:

105

AN XY:

71314

show subpopulations

Gnomad AFR exome

AF:

0.000329

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00375

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.000997

GnomAD4 exome

AF:

0.00128

AC:

702

AN:

550262

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

427

AN XY:

297868

show subpopulations

Gnomad4 AFR exome

AF:

0.000253

Gnomad4 AMR exome

AF:

0.000259

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00339

Gnomad4 FIN exome

AF:

0.00108

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.000840

AC:

128

AN:

152378

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.000999

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000717

Hom.:

Bravo

AF:

0.000578

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.00207

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CHEK1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 08, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.070

DANN

Benign

0.86

DEOGEN2

Benign

0.0059

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

1.0

REVEL

Benign

0.094

Sift

Benign

0.66

Polyphen

0.0

Vest4

0.15

MVP

0.21

ClinPred

0.020

GERP RS

-6.7

gMVP

0.48

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