rs565416

Variant names:

• chr11-125632572-C-T
• rs565416
• NM_001114122.3:c.425-591C>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.425-591C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,934 control chromosomes in the GnomAD database, including 7,965 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 (7965 hom., cov: 32)
• Consequence: CHEK1 NM_001114122.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHEK1	NM_001114122.3	c.425-591C>T		intron_variant	Intron 5 of 12	ENST00000438015.7	NP_001107594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHEK1	ENST00000438015.7	c.425-591C>T		intron_variant	Intron 5 of 12	5	NM_001114122.3	ENSP00000388648.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48366 AN: 151818 Hom.: 7952 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.319 AC: 48407 AN: 151934 Hom.: 7965 Cov.: 32 AF XY: 0.319 AC XY: 23652 AN XY: 74242

African (AFR) AF: 0.373 AC: 15468 AN: 41428

American (AMR) AF: 0.246 AC: 3765 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1069 AN: 3466

East Asian (EAS) AF: 0.421 AC: 2178 AN: 5168

South Asian (SAS) AF: 0.350 AC: 1689 AN: 4820

European-Finnish (FIN) AF: 0.288 AC: 3028 AN: 10518

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

European-Non Finnish (NFE) AF: 0.300 AC: 20360 AN: 67940

Other (OTH) AF: 0.306 AC: 646 AN: 2108

Alfa AF: 0.309 Hom.: 976

Bravo AF: 0.316

Asia WGS AF: 0.358 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.39
PhyloP100		-0.096
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: rs565416; hg19: chr11-125502467;