Variant 11-125625837-A-G 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.77A>G(p.Asn26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 702,610 control chromosomes in the GnomAD database, including 6 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 Benign (★). Synonymous variant affecting the same amino acid position (i.e. N26N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 6 hom. )

Consequence

CHEK1
ENST00000427383.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.58

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=0.004249066).

BP6

Variant 11-125625837-A-G is Benign according to our data. Variant chr11-125625837-A-G is described in ClinVar as [Benign]. Clinvar id is 3043887.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 374 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHEK1	NM_001114122.3 linkuse as main transcript	c.-196A>G		5_prime_UTR_variant	1/13	ENST00000438015.7
LOC118567325	NR_170378.1 linkuse as main transcript	n.58T>C		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.-196A>G		5_prime_UTR_variant	1/13	5	NM_001114122.3	P1	O14757-1
	ENST00000686400.2 linkuse as main transcript	n.77T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00245

AC:

373

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00244

AC:

319

AN:

130710

Hom.:

AF XY:

0.00254

AC XY:

181

AN XY:

71364

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.000657

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00210

Gnomad FIN exome

AF:

0.00985

Gnomad NFE exome

AF:

0.00376

Gnomad OTH exome

AF:

0.00299

GnomAD4 exome

AF:

0.00326

AC:

1794

AN:

550236

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

964

AN XY:

297858

show subpopulations

Gnomad4 AFR exome

AF:

0.000506

Gnomad4 AMR exome

AF:

0.000835

Gnomad4 ASJ exome

AF:

0.0000499

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.0110

Gnomad4 NFE exome

AF:

0.00362

Gnomad4 OTH exome

AF:

0.00275

GnomAD4 genome

AF:

0.00245

AC:

374

AN:

152374

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

197

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.0111

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00215

Hom.:

Bravo

AF:

0.00181

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00234

AC:

ExAC

AF:

0.00149

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CHEK1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 08, 2019

This variant is classified as 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

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.27

DANN

Benign

0.89

DEOGEN2

Benign

0.0049

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

0.65

REVEL

Benign

0.095

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.092

MVP

0.32

ClinPred

0.038

GERP RS

-4.1

gMVP

0.094

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