rs116191495

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001114122.3(CHEK1):c.-253A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 694,784 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0065 ( 16 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 6 hom. )

Consequence

CHEK1
NM_001114122.3 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.33

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CHEK1 links:

ENSG00000288907 (HGNC:):

ENSG00000288907 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034166276).

BP6

Variant 11-125625780-A-T is Benign according to our data. Variant chr11-125625780-A-T is described in ClinVar as [Benign]. Clinvar id is 3044253.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00647 (986/152302) while in subpopulation AFR AF = 0.0219 (910/41562). AF 95% confidence interval is 0.0207. There are 16 homozygotes in GnomAd4. There are 462 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 986 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHEK1	NM_001114122.3 link	c.-253A>T		5_prime_UTR_variant	Exon 1 of 13	ENST00000438015.7	NP_001107594.1	O14757-1B4DT73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHEK1	ENST00000438015.7 link	c.-253A>T		5_prime_UTR_variant	Exon 1 of 13	5	NM_001114122.3	ENSP00000388648.1		O14757-1

Frequencies

GnomAD3 genomes

AF:

0.00648

AC:

986

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00134

AC:

175

AN:

130182

AF XY:

0.00125

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000603

Gnomad OTH exome

AF:

0.00100

GnomAD4 exome

AF:

0.000841

AC:

456

AN:

542482

Hom.:

Cov.:

AF XY:

0.000736

AC XY:

215

AN XY:

292160

show subpopulations

African (AFR)

AF:

0.0222

AC:

347

AN:

15612

American (AMR)

AF:

0.00127

AC:

AN:

34520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19930

East Asian (EAS)

AF:

0.00

AC:

AN:

31856

South Asian (SAS)

AF:

0.0000319

AC:

AN:

62682

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33096

Middle Eastern (MID)

AF:

0.000494

AC:

AN:

4046

European-Non Finnish (NFE)

AF:

0.0000741

AC:

AN:

310594

Other (OTH)

AF:

0.00126

AC:

AN:

30146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

110

138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00647

AC:

986

AN:

152302

Hom.:

Cov.:

AF XY:

0.00620

AC XY:

462

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0219

AC:

910

AN:

41562

American (AMR)

AF:

0.00392

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68010

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

100

149

199

249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00312

Hom.:

Bravo

AF:

0.00726

ExAC

AF:

0.000360

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CHEK1-related disorder

Benign:1

Dec 23, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Benign

8.0

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

Eigen

Benign

-0.85

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

PhyloP100

1.3

PROVEAN

Benign

-0.54

REVEL

Benign

0.083

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.41

Vest4

0.31

MVP

0.44

ClinPred

0.089

GERP RS

-1.3

PromoterAI

0.041

Neutral

(source)

gMVP

0.43

Mutation Taster

=97/3

polymorphism

(source)

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

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rs116191495

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over