dbSNP rs9947295: GNAL:c.624+5488C>T (chr18-11759433-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182978.4(GNAL):c.624+5488C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,284 control chromosomes in the GnomAD database, including 5,475 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 5475 hom., cov: 33)

Consequence

GNAL
NM_182978.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.211

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

dystonia 25
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Ambry Genetics

GNAL links:

ENSG00000286812 (HGNC:):

ENSG00000286812 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_182978.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182978.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GNAL	NM_182978.4	MANE Select	c.624+5488C>T	intron	N/A	NP_892023.1	P38405-2
GNAL	NM_001369387.1	MANE Plus Clinical	c.393+5488C>T	intron	N/A	NP_001356316.1	A8K1Y9
GNAL	NM_001142339.3		c.393+5488C>T	intron	N/A	NP_001135811.1	A8K1Y9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GNAL	ENST00000334049.11	TSL:1 MANE Select	c.624+5488C>T	intron	N/A	ENSP00000334051.5	P38405-2
GNAL	ENST00000423027.8	TSL:1 MANE Plus Clinical	c.393+5488C>T	intron	N/A	ENSP00000408489.2	P38405-1
GNAL	ENST00000535121.5	TSL:1	c.393+5488C>T	intron	N/A	ENSP00000439023.1	P38405-1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31595

AN:

152166

Hom.:

5451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.474

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.0415

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0379

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.208

AC:

31667

AN:

152284

Hom.:

5475

Cov.:

AF XY:

0.202

AC XY:

15047

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.475

AC:

19716

AN:

41530

American (AMR)

AF:

0.124

AC:

1894

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

585

AN:

3470

East Asian (EAS)

AF:

0.0414

AC:

215

AN:

5190

South Asian (SAS)

AF:

0.110

AC:

530

AN:

4834

European-Finnish (FIN)

AF:

0.0379

AC:

403

AN:

10622

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7730

AN:

68010

Other (OTH)

AF:

0.188

AC:

398

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1092

2185

3277

4370

5462

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.143

Hom.:

8011

Bravo

AF:

0.225

Asia WGS

AF:

0.100

AC:

350

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.94

(source)

DANN

Benign

0.19

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over