Genetic Variant CHEK1:p.Gly77Val (chr11-125627771-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001114122.3(CHEK1):c.230G>T(p.Gly77Val) variant causes a missense change. The variant allele was found at a frequency of 0.000187 in 1,612,834 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 4 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 1 hom. )

Consequence

CHEK1
NM_001114122.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 7.13

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027391374).

BS2

High AC in GnomAd4 at 194 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114122.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHEK1	NM_001114122.3	MANE Select	c.230G>T	p.Gly77Val	missense	Exon 3 of 13	NP_001107594.1	O14757-1
CHEK1	NM_001114121.2		c.230G>T	p.Gly77Val	missense	Exon 3 of 14	NP_001107593.1	O14757-1
CHEK1	NM_001274.5		c.230G>T	p.Gly77Val	missense	Exon 3 of 13	NP_001265.2	O14757-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHEK1	ENST00000438015.7	TSL:5 MANE Select	c.230G>T	p.Gly77Val	missense	Exon 3 of 13	ENSP00000388648.1	O14757-1
CHEK1	ENST00000428830.6	TSL:1	c.230G>T	p.Gly77Val	missense	Exon 3 of 14	ENSP00000412504.2	O14757-1
CHEK1	ENST00000534070.5	TSL:1	c.230G>T	p.Gly77Val	missense	Exon 3 of 13	ENSP00000435371.1	O14757-1

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

194

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0127

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000386

AC:

AN:

251008

AF XY:

0.000339

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000739

AC:

108

AN:

1460656

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

726662

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33436

American (AMR)

AF:

0.00237

AC:

106

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.00

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5144

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111790

Other (OTH)

AF:

0.0000166

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00127

AC:

194

AN:

152178

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.0127

AC:

194

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00130

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

CHEK1-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.026

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

7.1

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.40

Sift

Benign

0.061

Sift4G

Benign

0.16

Polyphen

0.84

Vest4

0.95

MutPred

0.30

Loss of sheet (P = 0.0817)

MVP

0.83

MPC

1.4

ClinPred

0.19

GERP RS

4.6

Varity_R

0.91

Mutation Taster

=59/41

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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