18-11753861-A-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_182978.4(GNAL):āc.540A>Gā(p.Pro180=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,609,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00028 ( 0 hom., cov: 33)
Exomes š: 0.000020 ( 0 hom. )
Consequence
GNAL
NM_182978.4 synonymous
NM_182978.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.188
Genes affected
GNAL (HGNC:4388): (G protein subunit alpha L) This gene encodes a stimulatory G protein alpha subunit which mediates odorant signaling in the olfactory epithelium. This protein couples dopamine type 1 receptors and adenosine A2A receptors and is widely expressed in the central nervous system. Mutations in this gene have been associated with dystonia 25 and this gene is located in a susceptibility region for bipolar disorder and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 18-11753861-A-G is Benign according to our data. Variant chr18-11753861-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 526226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.188 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000282 (43/152308) while in subpopulation AFR AF= 0.000986 (41/41574). AF 95% confidence interval is 0.000747. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 43 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAL | NM_182978.4 | c.540A>G | p.Pro180= | synonymous_variant | 4/12 | ENST00000334049.11 | |
GNAL | NM_001369387.1 | c.309A>G | p.Pro103= | synonymous_variant | 4/12 | ENST00000423027.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAL | ENST00000334049.11 | c.540A>G | p.Pro180= | synonymous_variant | 4/12 | 1 | NM_182978.4 | ||
GNAL | ENST00000423027.8 | c.309A>G | p.Pro103= | synonymous_variant | 4/12 | 1 | NM_001369387.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000269 AC: 41AN: 152190Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251416Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135906
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GnomAD4 exome AF: 0.0000199 AC: 29AN: 1456972Hom.: 0 Cov.: 28 AF XY: 0.0000179 AC XY: 13AN XY: 725274
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GnomAD4 genome AF: 0.000282 AC: 43AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28AN XY: 74476
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dystonic disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2023 | - - |
GNAL-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 11, 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). - |
Dystonia 25 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 04, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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