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18-11689611-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_182978.4(GNAL):c.48G>A(p.Gly16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,347,028 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

GNAL
NM_182978.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0420
Variant links:
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-11689611-G-A is Benign according to our data. Variant chr18-11689611-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1112127.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.042 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0014 (212/151968) while in subpopulation AFR AF= 0.00501 (208/41490). AF 95% confidence interval is 0.00446. There are 0 homozygotes in gnomad4. There are 96 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 213 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GNALNM_182978.4 linkuse as main transcriptc.48G>A p.Gly16= synonymous_variant 1/12 ENST00000334049.11
GNALXM_006722324.4 linkuse as main transcriptc.48G>A p.Gly16= synonymous_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GNALENST00000334049.11 linkuse as main transcriptc.48G>A p.Gly16= synonymous_variant 1/121 NM_182978.4 P38405-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00140
AC:
213
AN:
151860
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00503
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000272
AC:
1
AN:
3672
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
2300
show subpopulations
Gnomad AFR exome
AF:
0.00962
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000150
AC:
179
AN:
1195060
Hom.:
2
Cov.:
30
AF XY:
0.000151
AC XY:
88
AN XY:
581020
show subpopulations
Gnomad4 AFR exome
AF:
0.00638
Gnomad4 AMR exome
AF:
0.000532
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000213
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000403
Gnomad4 OTH exome
AF:
0.000389
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00140
AC:
212
AN:
151968
Hom.:
0
Cov.:
33
AF XY:
0.00129
AC XY:
96
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.00501
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000854
Hom.:
0
Bravo
AF:
0.00142
Asia WGS
AF:
0.000882
AC:
3
AN:
3416

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Dystonic disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
6.9
Dann
Benign
0.96

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs543230597; hg19: chr18-11689610; API