rs70937047
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001126049.2(KLLN):c.-671A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000275 in 181,608 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.00030 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
KLLN
NM_001126049.2 5_prime_UTR
NM_001126049.2 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.586
Genes affected
KLLN (HGNC:37212): (killin, p53 regulated DNA replication inhibitor) The protein encoded by this intronless gene is found in the nucleus, where it can inhibit DNA synthesis and promote S phase arrest coupled to apoptosis. The expression of this DNA binding protein is upregulated by transcription factor p53. [provided by RefSeq, Dec 2012]
PTEN (HGNC:9588): (phosphatase and tensin homolog) This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 10-87863158-T-C is Benign according to our data. Variant chr10-87863158-T-C is described in ClinVar as [Benign]. Clinvar id is 127667.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr10-87863158-T-C is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd at 46 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLLN | NM_001126049.2 | c.-671A>G | 5_prime_UTR_variant | 1/1 | ENST00000445946.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLLN | ENST00000445946.5 | c.-671A>G | 5_prime_UTR_variant | 1/1 | NM_001126049.2 | P1 | |||
PTEN | ENST00000688308.1 | c.-17+45T>C | intron_variant | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000302 AC: 46AN: 152088Hom.: 1 Cov.: 32
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GnomAD4 exome AF: 0.000136 AC: 4AN: 29402Hom.: 0 Cov.: 0 AF XY: 0.000213 AC XY: 3AN XY: 14062
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2019 | This variant is associated with the following publications: (PMID: 25669429, 30311380) - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 20, 2018 | - - |
PTEN hamartoma tumor syndrome Benign:1
Benign, reviewed by expert panel | curation | Clingen PTEN Variant Curation Expert Panel, Clingen | Jun 02, 2017 | PTEN c.-1311T>C (NC_000010.10:g.89622915T>C) meets criteria to be classified as benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). BA1: Allele frequency of 0.0142 (1.42%, 23/1618 alleles) in the African subpopulation of the gnomAD cohort. (PMID 27535533) - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at