chr2-217804450-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001387777.1(TNS1):c.*9C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,614,024 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0033 ( 2 hom., cov: 31)
Exomes 𝑓: 0.0041 ( 29 hom. )
Consequence
TNS1
NM_001387777.1 3_prime_UTR
NM_001387777.1 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.90
Genes affected
TNS1 (HGNC:11973): (tensin 1) The protein encoded by this gene localizes to focal adhesions, regions of the plasma membrane where the cell attaches to the extracellular matrix. This protein crosslinks actin filaments and contains a Src homology 2 (SH2) domain, which is often found in molecules involved in signal transduction. This protein is a substrate of calpain II. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 2-217804450-G-A is Benign according to our data. Variant chr2-217804450-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041622.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00409 (5978/1461750) while in subpopulation MID AF= 0.038 (219/5764). AF 95% confidence interval is 0.0339. There are 29 homozygotes in gnomad4_exome. There are 3054 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 507 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNS1 | NM_001387777.1 | c.*9C>T | 3_prime_UTR_variant | 33/33 | ENST00000682258.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNS1 | ENST00000682258.1 | c.*9C>T | 3_prime_UTR_variant | 33/33 | NM_001387777.1 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00335 AC: 509AN: 152156Hom.: 2 Cov.: 31
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GnomAD3 exomes AF: 0.00390 AC: 980AN: 251310Hom.: 6 AF XY: 0.00418 AC XY: 568AN XY: 135822
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GnomAD4 exome AF: 0.00409 AC: 5978AN: 1461750Hom.: 29 Cov.: 31 AF XY: 0.00420 AC XY: 3054AN XY: 727182
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GnomAD4 genome AF: 0.00333 AC: 507AN: 152274Hom.: 2 Cov.: 31 AF XY: 0.00310 AC XY: 231AN XY: 74462
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
TNS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 01, 2019 | 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). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at