18-11689815-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_182978.4(GNAL):c.252G>A(p.Glu84Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,537,772 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 9 hom. )

Consequence

GNAL
NM_182978.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.28

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]

GNAL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 18-11689815-G-A is Benign according to our data. Variant chr18-11689815-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1175112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-11689815-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00181 (275/152088) while in subpopulation AMR AF= 0.00347 (53/15276). AF 95% confidence interval is 0.00272. There are 0 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 275 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAL	NM_182978.4 link	c.252G>A	p.Glu84Glu	synonymous_variant	Exon 1 of 12	ENST00000334049.11	NP_892023.1	P38405-2
GNAL	XM_006722324.4 link	c.252G>A	p.Glu84Glu	synonymous_variant	Exon 1 of 6		XP_006722387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAL	ENST00000334049.11 link	c.252G>A	p.Glu84Glu	synonymous_variant	Exon 1 of 12	1	NM_182978.4	ENSP00000334051.5		P38405-2
GNAL	ENST00000585590.1 link	n.126G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00180

AC:

274

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00260

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00179

AC:

253

AN:

141000

Hom.:

AF XY:

0.00201

AC XY:

158

AN XY:

78484

show subpopulations

Gnomad AFR exome

AF:

0.000414

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.000901

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00308

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00246

Gnomad OTH exome

AF:

0.00161

GnomAD4 exome

AF:

0.00243

AC:

3364

AN:

1385684

Hom.:

Cov.:

AF XY:

0.00245

AC XY:

1679

AN XY:

685442

show subpopulations

Gnomad4 AFR exome

AF:

0.000309

Gnomad4 AMR exome

AF:

0.00158

Gnomad4 ASJ exome

AF:

0.000774

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00326

Gnomad4 FIN exome

AF:

0.000136

Gnomad4 NFE exome

AF:

0.00266

Gnomad4 OTH exome

AF:

0.00235

GnomAD4 genome

AF:

0.00181

AC:

275

AN:

152088

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

137

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.00347

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00260

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.00181

Asia WGS

AF:

0.00146

AC:

AN:

3430

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GNAL: BP4, BP7, BS1 -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

GNAL-related disorder

Benign:1

Jan 30, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Dystonic disorder

Benign:1

Jan 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over