chr18-11689813-G-GAGGAGCGCGAGGCGGCCA
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2
The NM_182978.4(GNAL):c.266_283dup(p.Ala89_Ala94dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000388 in 1,537,556 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. E84E) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00037 ( 1 hom. )
Consequence
GNAL
NM_182978.4 inframe_insertion
NM_182978.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.81
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 -8 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_182978.4.
BP6
?
Variant 18-11689813-G-GAGGAGCGCGAGGCGGCCA is Benign according to our data. Variant chr18-11689813-G-GAGGAGCGCGAGGCGGCCA is described in ClinVar as [Likely_benign]. Clinvar id is 1299265.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000513 (78/152110) while in subpopulation SAS AF= 0.00331 (16/4830). AF 95% confidence interval is 0.00208. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 77 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAL | NM_182978.4 | c.266_283dup | p.Ala89_Ala94dup | inframe_insertion | 1/12 | ENST00000334049.11 | |
GNAL | XM_006722324.4 | c.266_283dup | p.Ala89_Ala94dup | inframe_insertion | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAL | ENST00000334049.11 | c.266_283dup | p.Ala89_Ala94dup | inframe_insertion | 1/12 | 1 | NM_182978.4 | ||
GNAL | ENST00000585590.1 | n.140_157dup | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000507 AC: 77AN: 152002Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000574 AC: 80AN: 139488Hom.: 1 AF XY: 0.000760 AC XY: 59AN XY: 77628
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GnomAD4 exome AF: 0.000374 AC: 518AN: 1385446Hom.: 1 Cov.: 32 AF XY: 0.000465 AC XY: 319AN XY: 685340
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | GNAL: BS1 - |
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at