chr18-11689700-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_182978.4(GNAL):c.137G>A(p.Arg46Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,472,928 control chromosomes in the GnomAD database, including 16,272 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.12 ( 1276 hom., cov: 33)
Exomes 𝑓: 0.15 ( 14996 hom. )
Consequence
GNAL
NM_182978.4 missense
NM_182978.4 missense
Scores
1
14
Clinical Significance
Conservation
PhyloP100: 0.0150
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0015120506).
BP6
?
Variant 18-11689700-G-A is Benign according to our data. Variant chr18-11689700-G-A is described in ClinVar as [Benign]. Clinvar id is 1169620.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAL | NM_182978.4 | c.137G>A | p.Arg46Lys | missense_variant | 1/12 | ENST00000334049.11 | |
GNAL | XM_006722324.4 | c.137G>A | p.Arg46Lys | missense_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAL | ENST00000334049.11 | c.137G>A | p.Arg46Lys | missense_variant | 1/12 | 1 | NM_182978.4 | ||
GNAL | ENST00000585590.1 | n.11G>A | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.122 AC: 18463AN: 151896Hom.: 1277 Cov.: 33
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GnomAD3 exomes AF: 0.115 AC: 9137AN: 79358Hom.: 617 AF XY: 0.116 AC XY: 5272AN XY: 45594
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GnomAD4 exome AF: 0.146 AC: 192714AN: 1320924Hom.: 14996 Cov.: 32 AF XY: 0.145 AC XY: 94237AN XY: 651018
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GnomAD4 genome ? AF: 0.121 AC: 18459AN: 152004Hom.: 1276 Cov.: 33 AF XY: 0.119 AC XY: 8812AN XY: 74324
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dystonic disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
P
PrimateAI
Pathogenic
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at