ENST00000427383.6:c.77A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). 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 no assertion criteria provided B:1

Conservation

PhyloP100: -2.58

Publications

1 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 -9 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 no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 374 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHEK1	NM_001114122.3 link	c.-196A>G		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.-196A>G		5_prime_UTR_variant	Exon 1 of 13	5	NM_001114122.3	ENSP00000388648.1		O14757-1

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

GnomAD2 exomes

AF:

0.00244

AC:

319

AN:

130710

AF XY:

0.00254

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 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

African (AFR)

AF:

0.000506

AC:

AN:

15808

American (AMR)

AF:

0.000835

AC:

AN:

34716

Ashkenazi Jewish (ASJ)

AF:

0.0000499

AC:

AN:

20026

East Asian (EAS)

AF:

0.00

AC:

AN:

32104

South Asian (SAS)

AF:

0.00245

AC:

154

AN:

62770

European-Finnish (FIN)

AF:

0.0110

AC:

365

AN:

33188

Middle Eastern (MID)

AF:

0.00172

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.00362

AC:

1146

AN:

316948

Other (OTH)

AF:

0.00275

AC:

AN:

30600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

112

224

337

449

561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00245

AC:

374

AN:

152374

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

197

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.000673

AC:

AN:

41598

American (AMR)

AF:

0.000588

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00103

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0111

AC:

118

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00310

AC:

211

AN:

68036

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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: no assertion criteria provided

LINK: link

Submissions by phenotype

CHEK1-related disorder

Benign:1

Nov 08, 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

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.27

(source)

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

PhyloP100

-2.6

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

PromoterAI

-0.049

Neutral

(source)

gMVP

0.094

Mutation Taster

=98/2

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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ENST00000427383.6:c.77A>G

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