rs515255

Variant names:

• chr11-125627250-G-A
• rs515255
• NM_001114122.3:c.66-357G>A

Variant summary

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

The NM_001114122.3(CHEK1):​c.66-357G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,966 control chromosomes in the GnomAD database, including 16,810 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 0.46 (16810 hom., cov: 32)
• Consequence: CHEK1 NM_001114122.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHEK1	NM_001114122.3	c.66-357G>A		intron_variant	Intron 2 of 12	ENST00000438015.7	NP_001107594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHEK1	ENST00000438015.7	c.66-357G>A		intron_variant	Intron 2 of 12	5	NM_001114122.3	ENSP00000388648.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69429 AN: 151848 Hom.: 16805 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.457 AC: 69444 AN: 151966 Hom.: 16810 Cov.: 32 AF XY: 0.459 AC XY: 34060 AN XY: 74278

African (AFR) AF: 0.283 AC: 11723 AN: 41428

American (AMR) AF: 0.570 AC: 8698 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1728 AN: 3472

East Asian (EAS) AF: 0.401 AC: 2075 AN: 5174

South Asian (SAS) AF: 0.550 AC: 2642 AN: 4808

European-Finnish (FIN) AF: 0.490 AC: 5167 AN: 10550

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35795 AN: 67962

Other (OTH) AF: 0.473 AC: 997 AN: 2110

Alfa AF: 0.486 Hom.: 5032

Bravo AF: 0.454

Asia WGS AF: 0.478 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.62
PhyloP100		0.48
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: rs515255; hg19: chr11-125497145;