11-125646169-C-T

Variant names:

• chr11-125646169-C-T
• rs3731459
• NM_001114122.3:c.1233+1526C>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.1233+1526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 151,986 control chromosomes in the GnomAD database, including 522 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 0.076 (522 hom., cov: 32)
• Consequence: CHEK1 NM_001114122.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHEK1	NM_001114122.3	c.1233+1526C>T		intron_variant	Intron 11 of 12	ENST00000438015.7	NP_001107594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHEK1	ENST00000438015.7	c.1233+1526C>T		intron_variant	Intron 11 of 12	5	NM_001114122.3	ENSP00000388648.1

Frequencies

GnomAD3 genomes AF: 0.0762 AC: 11573 AN: 151870 Hom.: 520 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0862

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

GnomAD4 genome AF: 0.0763 AC: 11593 AN: 151986 Hom.: 522 Cov.: 32 AF XY: 0.0742 AC XY: 5514 AN XY: 74278

African (AFR) AF: 0.120 AC: 4955 AN: 41436

American (AMR) AF: 0.0515 AC: 786 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5184

South Asian (SAS) AF: 0.0513 AC: 247 AN: 4814

European-Finnish (FIN) AF: 0.0444 AC: 468 AN: 10544

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0653 AC: 4434 AN: 67950

Other (OTH) AF: 0.0844 AC: 178 AN: 2110

Alfa AF: 0.0685 Hom.: 1206

Bravo AF: 0.0790

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.41
PhyloP100		-0.39
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: rs3731459; hg19: chr11-125516064;