rs377502057
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000455.5(STK11):c.598-7G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,578,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000455.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.598-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000326873.12 | |||
STK11 | NM_001407255.1 | c.598-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
STK11 | NR_176325.1 | n.1865-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.598-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000610 AC: 12AN: 196798Hom.: 0 AF XY: 0.0000745 AC XY: 8AN XY: 107438
GnomAD4 exome AF: 0.000118 AC: 169AN: 1426338Hom.: 0 Cov.: 32 AF XY: 0.000106 AC XY: 75AN XY: 705886
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
not provided Benign:5
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jan 16, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Peutz-Jeghers syndrome Benign:5
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Aug 10, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Apr 12, 2023 | This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 30, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 29, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 11, 2014 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Breast and/or ovarian cancer Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Sep 30, 2022 | - - |
STK11-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 25, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Endometrial carcinoma Benign:1
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The STK11 c.598-7G>A variant was not identified in the literature nor was it identified in MutDB, Zhejiang University Database or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs377502057) “With Likely benign allele”, ClinVar (classified as likely benign by Invitae, Counsyl, Quest Diagnostics Nichols Institute San Juan Capistrano, and Color Genomics Inc.), Cosmic (1x in a carcinoma of the prostate), and LOVD 3.0 (1x). The variant was also identified in control databases in 17 of 223852 chromosomes at a frequency of 0.00008 (Genome Aggregation Database Feb 27, 2017); the variant was observed in the following populations: European Non-Finnish in 14 of 97910 chromosomes (freq: 0.0001), Latino in 1 of 29348 chromosomes (freq: 0.00003), and South Asian in 2 of 26370 chromosomes (freq: 0.00008), while not observed in the African, Other, Ashkenazi Jewish, East Asian or Finnish populations. The c.598-7G>A variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. Although positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at