11-125625824-G-A
Position:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The ENST00000427383.6(CHEK1):c.64G>A(p.Gly22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 702,604 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0044 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00057 ( 1 hom. )
Consequence
CHEK1
ENST00000427383.6 missense
ENST00000427383.6 missense
Scores
2
1
12
Clinical Significance
Conservation
PhyloP100: -0.387
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]
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=0.0036801398).
BP6
Variant 11-125625824-G-A is Benign according to our data. Variant chr11-125625824-G-A is described in ClinVar as [Benign]. Clinvar id is 3052481.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 668 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHEK1 | NM_001114122.3 | c.-209G>A | 5_prime_UTR_variant | 1/13 | ENST00000438015.7 | ||
LOC118567325 | NR_170378.1 | n.71C>T | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHEK1 | ENST00000438015.7 | c.-209G>A | 5_prime_UTR_variant | 1/13 | 5 | NM_001114122.3 | P1 | ||
ENST00000686400.2 | n.90C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.00439 AC: 668AN: 152250Hom.: 6 Cov.: 33
GnomAD3 genomes
AF:
AC:
668
AN:
152250
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000964 AC: 126AN: 130738Hom.: 0 AF XY: 0.000588 AC XY: 42AN XY: 71380
GnomAD3 exomes
AF:
AC:
126
AN:
130738
Hom.:
AF XY:
AC XY:
42
AN XY:
71380
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000567 AC: 312AN: 550236Hom.: 1 Cov.: 0 AF XY: 0.000430 AC XY: 128AN XY: 297852
GnomAD4 exome
AF:
AC:
312
AN:
550236
Hom.:
Cov.:
0
AF XY:
AC XY:
128
AN XY:
297852
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00438 AC: 668AN: 152368Hom.: 6 Cov.: 33 AF XY: 0.00444 AC XY: 331AN XY: 74508
GnomAD4 genome
AF:
AC:
668
AN:
152368
Hom.:
Cov.:
33
AF XY:
AC XY:
331
AN XY:
74508
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
0
ExAC
AF:
AC:
7
Asia WGS
AF:
AC:
3
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 26, 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
B
Vest4
MVP
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at