11-125625851-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000427383.6(CHEK1):c.91C>G(p.Pro31Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 702,562 control chromosomes in the GnomAD database, including 3,088 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 1468 hom., cov: 33)

Exomes 𝑓: 0.066 ( 1620 hom. )

Consequence

CHEK1
ENST00000427383.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.79

Publications

14 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: Unknown Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: Unknown 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=0.00483346).

BP6

Variant 11-125625851-C-G is Benign according to our data. Variant chr11-125625851-C-G is described in ClinVar as Benign. ClinVar VariationId is 3055541.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427383.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHEK1	NM_001114122.3	MANE Select	c.-182C>G	5_prime_UTR	Exon 1 of 13	NP_001107594.1	O14757-1
CHEK1	NM_001114121.2		c.-182C>G	5_prime_UTR	Exon 1 of 14	NP_001107593.1	O14757-1
CHEK1	NM_001244846.1		c.-182C>G	5_prime_UTR	Exon 1 of 12	NP_001231775.1	B4DT73

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHEK1	ENST00000427383.6	TSL:1	c.91C>G	p.Pro31Ala	missense	Exon 1 of 12	ENSP00000391090.2	E7EPP6
CHEK1	ENST00000438015.7	TSL:5 MANE Select	c.-182C>G		5_prime_UTR	Exon 1 of 13	ENSP00000388648.1	O14757-1
CHEK1	ENST00000711049.1		c.91C>G	p.Pro31Ala	missense	Exon 1 of 13	ENSP00000518558.1	E7EPP6

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17100

AN:

152202

Hom.:

1465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.0667

Gnomad ASJ

AF:

0.0783

Gnomad EAS

AF:

0.0216

Gnomad SAS

AF:

0.0550

Gnomad FIN

AF:

0.0439

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0659

Gnomad OTH

AF:

0.112

GnomAD2 exomes

AF:

0.0657

AC:

8588

AN:

130658

AF XY:

0.0641

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.0453

Gnomad ASJ exome

AF:

0.0773

Gnomad EAS exome

AF:

0.0267

Gnomad FIN exome

AF:

0.0476

Gnomad NFE exome

AF:

0.0681

Gnomad OTH exome

AF:

0.0859

GnomAD4 exome

AF:

0.0663

AC:

36470

AN:

550242

Hom.:

1620

Cov.:

AF XY:

0.0639

AC XY:

19036

AN XY:

297860

show subpopulations

African (AFR)

AF:

0.245

AC:

3871

AN:

15806

American (AMR)

AF:

0.0492

AC:

1707

AN:

34716

Ashkenazi Jewish (ASJ)

AF:

0.0787

AC:

1577

AN:

20028

East Asian (EAS)

AF:

0.0182

AC:

585

AN:

32104

South Asian (SAS)

AF:

0.0490

AC:

3076

AN:

62772

European-Finnish (FIN)

AF:

0.0491

AC:

1628

AN:

33188

Middle Eastern (MID)

AF:

0.129

AC:

523

AN:

4070

European-Non Finnish (NFE)

AF:

0.0661

AC:

20958

AN:

316958

Other (OTH)

AF:

0.0832

AC:

2545

AN:

30600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

2210

4421

6631

8842

11052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.112

AC:

17131

AN:

152320

Hom.:

1468

Cov.:

AF XY:

0.109

AC XY:

8146

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.242

AC:

10037

AN:

41556

American (AMR)

AF:

0.0666

AC:

1019

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0783

AC:

272

AN:

3472

East Asian (EAS)

AF:

0.0218

AC:

113

AN:

5180

South Asian (SAS)

AF:

0.0548

AC:

265

AN:

4832

European-Finnish (FIN)

AF:

0.0439

AC:

467

AN:

10628

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0659

AC:

4484

AN:

68028

Other (OTH)

AF:

0.110

AC:

232

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

785

1569

2354

3138

3923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0503

Hom.:

Bravo

AF:

0.120

TwinsUK

AF:

0.0709

AC:

263

ALSPAC

AF:

0.0620

AC:

239

ExAC

AF:

0.0452

AC:

718

Asia WGS

AF:

0.0620

AC:

216

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CHEK1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.19

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.0052

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.0

PhyloP100

-3.8

PROVEAN

Benign

0.25

REVEL

Benign

0.049

Sift

Benign

0.19

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.031

ClinPred

0.0032

GERP RS

-3.3

PromoterAI

-0.094

Neutral

(source)

gMVP

0.12

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over