rs492510

Variant names:

• chr11-125627447-A-G
• rs492510
• NM_001114122.3:c.66-160A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-125627447-A-G
• chr11-125627447-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001114122.3(CHEK1):​c.66-160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,072 control chromosomes in the GnomAD database, including 12,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (12262 hom., cov: 32)
• Consequence: CHEK1 NM_001114122.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.484
• Publications: 18 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-125627447-A-G is Benign according to our data. Variant chr11-125627447-A-G is described in ClinVar as [Benign]. Clinvar id is 1243629.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHEK1	NM_001114122.3	c.66-160A>G		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.66-160A>G		intron_variant	Intron 2 of 12	5	NM_001114122.3	ENSP00000388648.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59911 AN: 151954 Hom.: 12239 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.394 AC: 59979 AN: 152072 Hom.: 12262 Cov.: 32 AF XY: 0.392 AC XY: 29158 AN XY: 74360

African (AFR) AF: 0.501 AC: 20756 AN: 41442

American (AMR) AF: 0.295 AC: 4506 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1334 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2195 AN: 5186

South Asian (SAS) AF: 0.401 AC: 1927 AN: 4810

European-Finnish (FIN) AF: 0.330 AC: 3489 AN: 10578

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24495 AN: 67984

Other (OTH) AF: 0.392 AC: 829 AN: 2114

Alfa AF: 0.365 Hom.: 1828

Bravo AF: 0.395

Asia WGS AF: 0.396 AC: 1378 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 27, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31904144) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.63
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs492510; hg19: chr11-125497342;