chr11-2166625-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000360.4(TH):c.977+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,578,486 control chromosomes in the GnomAD database, including 91,703 homozygotes. 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 Benign (★★).
Frequency
Consequence
NM_000360.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TH | NM_000360.4 | c.977+8C>G | splice_region_variant, intron_variant | ENST00000352909.8 | |||
TH | NM_199292.3 | c.1070+8C>G | splice_region_variant, intron_variant | ||||
TH | NM_199293.3 | c.1058+8C>G | splice_region_variant, intron_variant | ||||
TH | XM_011520335.3 | c.989+8C>G | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TH | ENST00000352909.8 | c.977+8C>G | splice_region_variant, intron_variant | 1 | NM_000360.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.272 AC: 41314AN: 152114Hom.: 6578 Cov.: 35
GnomAD3 exomes AF: 0.279 AC: 50436AN: 180986Hom.: 8120 AF XY: 0.278 AC XY: 27547AN XY: 98990
GnomAD4 exome AF: 0.335 AC: 478037AN: 1426256Hom.: 85125 Cov.: 78 AF XY: 0.331 AC XY: 233704AN XY: 706218
GnomAD4 genome AF: 0.271 AC: 41307AN: 152230Hom.: 6578 Cov.: 35 AF XY: 0.265 AC XY: 19748AN XY: 74434
ClinVar
Submissions by phenotype
Autosomal recessive DOPA responsive dystonia Benign:6
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | Feb 07, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 14, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jul 31, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 42% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 39. Only high quality variants are reported. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 14, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at