rs863224362
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000455.5(STK11):c.921-8G>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 0.0000214 in 1,541,568 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 Conflicting classifications of pathogenicity (no stars).
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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.921-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000326873.12 | |||
STK11 | NM_001407255.1 | c.921-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
STK11 | NR_176325.1 | n.2188-8G>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.921-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000193 AC: 3AN: 155770Hom.: 0 AF XY: 0.0000361 AC XY: 3AN XY: 83192
GnomAD4 exome AF: 0.0000216 AC: 30AN: 1389270Hom.: 0 Cov.: 31 AF XY: 0.0000190 AC XY: 13AN XY: 683368
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152298Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74462
ClinVar
Submissions by phenotype
Peutz-Jeghers syndrome Uncertain:2Benign:2
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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Dec 01, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 02, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 24, 2015 | - - |
Malignant tumor of breast Benign:1
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The STK11 c.921-8G>A variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (ID: rs863224362) as "With other allele", and in ClinVar (classified as likely benign by Invitae and Color; as uncertain significance by Myriad Women's Health).The variant was identified in control databases in 3 of 150676 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European population in 3 of 58874 chromosomes (freq: 0.00005), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The c.921-8G>A variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. However, 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. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Feb 22, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at