7-30633729-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002047.4(GARS1):c.2095-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,612,332 control chromosomes in the GnomAD database, including 303,617 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_002047.4 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 rank | MANE | Protein | UniProt |
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GARS1 | NM_002047.4 | c.2095-6C>T | splice_region_variant, intron_variant | Intron 16 of 16 | ENST00000389266.8 | NP_002038.2 | ||
GARS1 | NM_001316772.1 | c.1933-6C>T | splice_region_variant, intron_variant | Intron 16 of 16 | NP_001303701.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GARS1 | ENST00000389266.8 | c.2095-6C>T | splice_region_variant, intron_variant | Intron 16 of 16 | 1 | NM_002047.4 | ENSP00000373918.3 | |||
GARS1 | ENST00000675651.1 | c.2113-6C>T | splice_region_variant, intron_variant | Intron 16 of 16 | ENSP00000502513.1 | |||||
GARS1 | ENST00000675810.1 | c.1993-6C>T | splice_region_variant, intron_variant | Intron 15 of 15 | ENSP00000502743.1 | |||||
GARS1 | ENST00000675693.1 | c.1927-6C>T | splice_region_variant, intron_variant | Intron 17 of 17 | ENSP00000502174.1 | |||||
GARS1 | ENST00000675051.1 | c.1894-6C>T | splice_region_variant, intron_variant | Intron 16 of 16 | ENSP00000502296.1 | |||||
GARS1 | ENST00000674815.1 | c.1726-6C>T | splice_region_variant, intron_variant | Intron 16 of 16 | ENSP00000502799.1 | |||||
GARS1 | ENST00000674851.1 | c.1726-6C>T | splice_region_variant, intron_variant | Intron 17 of 17 | ENSP00000502451.1 | |||||
GARS1 | ENST00000444666.6 | n.*516-6C>T | splice_region_variant, intron_variant | Intron 17 of 17 | 3 | ENSP00000415447.2 | ||||
GARS1 | ENST00000674616.1 | n.*1809-6C>T | splice_region_variant, intron_variant | Intron 17 of 17 | ENSP00000502408.1 | |||||
GARS1 | ENST00000674643.1 | n.*1900-6C>T | splice_region_variant, intron_variant | Intron 16 of 16 | ENSP00000501636.1 | |||||
GARS1 | ENST00000674737.1 | n.*1433-6C>T | splice_region_variant, intron_variant | Intron 17 of 17 | ENSP00000502464.1 | |||||
GARS1 | ENST00000674807.1 | n.*368-6C>T | splice_region_variant, intron_variant | Intron 15 of 15 | ENSP00000502814.1 | |||||
GARS1 | ENST00000675529.1 | n.*1965-6C>T | splice_region_variant, intron_variant | Intron 17 of 17 | ENSP00000501655.1 | |||||
GARS1 | ENST00000675859.1 | n.*274-6C>T | splice_region_variant, intron_variant | Intron 14 of 14 | ENSP00000502033.1 | |||||
GARS1 | ENST00000676088.1 | n.*2037-6C>T | splice_region_variant, intron_variant | Intron 18 of 18 | ENSP00000501884.1 | |||||
GARS1 | ENST00000676140.1 | n.*1040-6C>T | splice_region_variant, intron_variant | Intron 16 of 16 | ENSP00000502571.1 | |||||
GARS1 | ENST00000676164.1 | n.*1546-6C>T | splice_region_variant, intron_variant | Intron 16 of 16 | ENSP00000501986.1 | |||||
GARS1 | ENST00000676210.1 | n.*1384-6C>T | splice_region_variant, intron_variant | Intron 17 of 17 | ENSP00000502373.1 | |||||
GARS1 | ENST00000676259.1 | n.*1527-6C>T | splice_region_variant, intron_variant | Intron 16 of 16 | ENSP00000501980.1 | |||||
GARS1 | ENST00000676403.1 | n.*180-6C>T | splice_region_variant, intron_variant | Intron 15 of 15 | ENSP00000502681.1 |
Frequencies
GnomAD3 genomes AF: 0.487 AC: 73957AN: 151770Hom.: 21507 Cov.: 30
GnomAD3 exomes AF: 0.560 AC: 139586AN: 249068Hom.: 41588 AF XY: 0.563 AC XY: 76049AN XY: 135166
GnomAD4 exome AF: 0.613 AC: 894881AN: 1460442Hom.: 282113 Cov.: 42 AF XY: 0.608 AC XY: 441967AN XY: 726596
GnomAD4 genome AF: 0.487 AC: 73958AN: 151890Hom.: 21504 Cov.: 30 AF XY: 0.484 AC XY: 35937AN XY: 74202
ClinVar
Submissions by phenotype
not specified Benign:5
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not provided Benign:2
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Charcot-Marie-Tooth disease type 2D Benign:2
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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. -
Neuronopathy, distal hereditary motor, type 5A Benign:2
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. -
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Charcot-Marie-Tooth disease Benign:1
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Distal spinal muscular atrophy Benign:1
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. -
Spinal muscular atrophy, infantile, James type Benign:1
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Charcot-Marie-Tooth disease type 2 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at