chr18-11697825-G-A

Variant names:

• chr18-11697825-G-A
• rs8087897
• NM_182978.4:c.376+7886G>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.376+7886G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,124 control chromosomes in the GnomAD database, including 9,521 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 0.27 (9521 hom., cov: 32)
• Consequence: GNAL NM_182978.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAL	NM_182978.4	c.376+7886G>A		intron_variant	Intron 1 of 11	ENST00000334049.11	NP_892023.1
GNAL	XM_006722324.4	c.376+7886G>A		intron_variant	Intron 1 of 5		XP_006722387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAL	ENST00000334049.11	c.376+7886G>A		intron_variant	Intron 1 of 11	1	NM_182978.4	ENSP00000334051.5
GNAL	ENST00000585590.1	n.251-4246G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40426 AN: 152006 Hom.: 9483 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.266 AC: 40513 AN: 152124 Hom.: 9521 Cov.: 32 AF XY: 0.259 AC XY: 19246 AN XY: 74384

African (AFR) AF: 0.638 AC: 26418 AN: 41434

American (AMR) AF: 0.147 AC: 2246 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3470

East Asian (EAS) AF: 0.0232 AC: 120 AN: 5180

South Asian (SAS) AF: 0.0817 AC: 394 AN: 4824

European-Finnish (FIN) AF: 0.0778 AC: 825 AN: 10602

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9193 AN: 67990

Other (OTH) AF: 0.237 AC: 500 AN: 2114

Alfa AF: 0.197 Hom.: 828

Bravo AF: 0.287

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.64
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs8087897; hg19: chr18-11697824;