Variant 18-11689700-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0150

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:

GNAL (HGNC:):

GNAL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
GNAL	NM_182978.4 linkuse as main transcript	c.137G>A	p.Arg46Lys	missense_variant	1/12	ENST00000334049.11	NP_892023.1	P38405-2
GNAL	XM_006722324.4 linkuse as main transcript	c.137G>A	p.Arg46Lys	missense_variant	1/6		XP_006722387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAL	ENST00000334049.11 linkuse as main transcript	c.137G>A	p.Arg46Lys	missense_variant	1/12	1	NM_182978.4	ENSP00000334051.5		P38405-2
GNAL	ENST00000585590.1 linkuse as main transcript	n.11G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18463

AN:

151896

Hom.:

1277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0837

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.0214

Gnomad SAS

AF:

0.0814

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.115

AC:

9137

AN:

79358

Hom.:

617

AF XY:

0.116

AC XY:

5272

AN XY:

45594

show subpopulations

Gnomad AFR exome

AF:

0.0925

Gnomad AMR exome

AF:

0.0706

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.00602

Gnomad SAS exome

AF:

0.0913

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.155

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.146

AC:

192714

AN:

1320924

Hom.:

14996

Cov.:

AF XY:

0.145

AC XY:

94237

AN XY:

651018

show subpopulations

Gnomad4 AFR exome

AF:

0.0831

Gnomad4 AMR exome

AF:

0.0841

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.0319

Gnomad4 SAS exome

AF:

0.0909

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.121

AC:

18459

AN:

152004

Hom.:

1276

Cov.:

AF XY:

0.119

AC XY:

8812

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0836

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.164

Gnomad4 EAS

AF:

0.0215

Gnomad4 SAS

AF:

0.0808

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.132

Hom.:

174

Bravo

AF:

0.121

ExAC

AF:

0.0469

AC:

2893

Asia WGS

AF:

0.0440

AC:

152

AN:

3450

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Dystonic disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.26

DANN

Benign

0.79

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.34

REVEL

Benign

0.20

Sift

Benign

0.70

Sift4G

Benign

0.13

Vest4

0.0090

MPC

1.3

ClinPred

0.0018

GERP RS

-3.4

gMVP

0.17

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