rs10468681

Variant names:

• chr18-11800067-C-A
• rs10468681
• NM_182978.4:c.625-24851C>A

Variant summary

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

The NM_182978.4(GNAL):​c.625-24851C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,028 control chromosomes in the GnomAD database, including 10,556 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 0.33 (10556 hom., cov: 32)
• Consequence: GNAL NM_182978.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 2 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

ACMG classification

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 = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAL	NM_182978.4	c.625-24851C>A		intron_variant	Intron 4 of 11	ENST00000334049.11	NP_892023.1
GNAL	NM_001369387.1	c.394-24851C>A		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.625-24851C>A		intron_variant	Intron 4 of 11	1	NM_182978.4	ENSP00000334051.5
GNAL	ENST00000423027.8	c.394-24851C>A		intron_variant	Intron 4 of 11	1	NM_001369387.1	ENSP00000408489.2

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50109 AN: 151910 Hom.: 10531 Cov.: 32

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.330 AC: 50169 AN: 152028 Hom.: 10556 Cov.: 32 AF XY: 0.328 AC XY: 24350 AN XY: 74334

African (AFR) AF: 0.602 AC: 24947 AN: 41432

American (AMR) AF: 0.194 AC: 2966 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1670 AN: 5168

South Asian (SAS) AF: 0.293 AC: 1412 AN: 4816

European-Finnish (FIN) AF: 0.169 AC: 1783 AN: 10560

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15414 AN: 67998

Other (OTH) AF: 0.306 AC: 647 AN: 2114

Alfa AF: 0.260 Hom.: 4335

Bravo AF: 0.345

Asia WGS AF: 0.275 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.054
DANN	Benign	0.36
PhyloP100		-1.5
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: rs10468681; hg19: chr18-11800066;