rs8098539

Variant names:

• chr18-11775387-A-G
• rs8098539
• NM_182978.4:c.624+21442A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-11775387-A-G
• chr18-11775387-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182978.4(GNAL):​c.624+21442A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,186 control chromosomes in the GnomAD database, including 20,079 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 0.46 (20079 hom., cov: 33)
• Consequence: GNAL NM_182978.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 4 publications found

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: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000286812 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAL	NM_182978.4	c.624+21442A>G		intron_variant	Intron 4 of 11	ENST00000334049.11	NP_892023.1
GNAL	NM_001369387.1	c.393+21442A>G		intron_variant	Intron 4 of 11	ENST00000423027.8	NP_001356316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAL	ENST00000334049.11	c.624+21442A>G		intron_variant	Intron 4 of 11	1	NM_182978.4	ENSP00000334051.5
GNAL	ENST00000423027.8	c.393+21442A>G		intron_variant	Intron 4 of 11	1	NM_001369387.1	ENSP00000408489.2

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69251 AN: 152068 Hom.: 20033 Cov.: 33

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.456 AC: 69332 AN: 152186 Hom.: 20079 Cov.: 33 AF XY: 0.450 AC XY: 33451 AN XY: 74406

African (AFR) AF: 0.828 AC: 34377 AN: 41526

American (AMR) AF: 0.286 AC: 4369 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1923 AN: 5174

South Asian (SAS) AF: 0.403 AC: 1945 AN: 4826

European-Finnish (FIN) AF: 0.204 AC: 2154 AN: 10578

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21727 AN: 68000

Other (OTH) AF: 0.432 AC: 914 AN: 2114

Alfa AF: 0.360 Hom.: 14556

Bravo AF: 0.477

Asia WGS AF: 0.366 AC: 1274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.51
PhyloP100		-0.021
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8098539; hg19: chr18-11775386;