Variant 11-125625780-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000427383.6(CHEK1):c.20A>T(p.Lys7Ile) variant causes a missense 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. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 16 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 6 hom. )

Consequence

CHEK1
ENST00000427383.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.33

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 986 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHEK1	NM_001114122.3 linkuse as main transcript	c.-253A>T		5_prime_UTR_variant	1/13	ENST00000438015.7
LOC118567325	NR_170378.1 linkuse as main transcript	n.115T>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHEK1	ENST00000438015.7 linkuse as main transcript	c.-253A>T		5_prime_UTR_variant	1/13	5	NM_001114122.3	P1	O14757-1
	ENST00000686400.2 linkuse as main transcript	n.134T>A		non_coding_transcript_exon_variant	1/1

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

GnomAD3 exomes

AF:

0.00134

AC:

175

AN:

130182

Hom.:

AF XY:

0.00125

AC XY:

AN XY:

71050

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 SAS 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

Gnomad4 AFR exome

AF:

0.0222

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000319

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000741

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00647

AC:

986

AN:

152302

Hom.:

Cov.:

AF XY:

0.00620

AC XY:

462

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0219

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00426

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: 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

Dec 23, 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Benign

8.0

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

MutationTaster

Benign

1.0

N;N

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

gMVP

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over