11-125654112-C-T

Variant names:

• chr11-125654112-C-T
• rs560087
• NM_001114122.3:c.1335+265C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001114122.3(CHEK1):​c.1335+265C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 150,882 control chromosomes in the GnomAD database, including 7,944 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (7944 hom., cov: 31)
• Consequence: CHEK1 NM_001114122.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHEK1	NM_001114122.3	c.1335+265C>T		intron_variant	Intron 12 of 12	ENST00000438015.7	NP_001107594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHEK1	ENST00000438015.7	c.1335+265C>T		intron_variant	Intron 12 of 12	5	NM_001114122.3	ENSP00000388648.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48204 AN: 150760 Hom.: 7931 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.307

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 48244 AN: 150882 Hom.: 7944 Cov.: 31 AF XY: 0.320 AC XY: 23558 AN XY: 73644

African (AFR) AF: 0.375 AC: 15380 AN: 41058

American (AMR) AF: 0.247 AC: 3737 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1069 AN: 3462

East Asian (EAS) AF: 0.426 AC: 2182 AN: 5126

South Asian (SAS) AF: 0.352 AC: 1674 AN: 4752

European-Finnish (FIN) AF: 0.292 AC: 3011 AN: 10314

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20346 AN: 67734

Other (OTH) AF: 0.307 AC: 642 AN: 2090

Alfa AF: 0.168 Hom.: 376

Bravo AF: 0.315

Asia WGS AF: 0.357 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.98
DANN	Benign	0.28
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs560087; hg19: chr11-125524007;