rs1477941

Variant names:

• chr18-11692441-C-G
• rs1477941
• NM_182978.4:c.376+2502C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-11692441-C-G
• chr18-11692441-C-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.376+2502C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,192 control chromosomes in the GnomAD database, including 8,002 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 0.23 (8002 hom., cov: 32)
• Consequence: GNAL NM_182978.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAL	NM_182978.4	c.376+2502C>G		intron_variant	Intron 1 of 11	ENST00000334049.11	NP_892023.1
GNAL	XM_006722324.4	c.376+2502C>G		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+2502C>G		intron_variant	Intron 1 of 11	1	NM_182978.4	ENSP00000334051.5
GNAL	ENST00000585590.1	n.250+2502C>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34650 AN: 152076 Hom.: 7974 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0903

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.228 AC: 34725 AN: 152192 Hom.: 8002 Cov.: 32 AF XY: 0.222 AC XY: 16538 AN XY: 74420

African (AFR) AF: 0.597 AC: 24772 AN: 41498

American (AMR) AF: 0.119 AC: 1812 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5188

South Asian (SAS) AF: 0.100 AC: 484 AN: 4822

European-Finnish (FIN) AF: 0.0537 AC: 570 AN: 10608

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0903 AC: 6138 AN: 68004

Other (OTH) AF: 0.189 AC: 398 AN: 2108

Alfa AF: 0.0705 Hom.: 142

Bravo AF: 0.246

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.54
PhyloP100		-0.34
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: rs1477941; hg19: chr18-11692440;