rs9947295

Variant names:

• chr18-11759433-C-T
• rs9947295
• NM_182978.4:c.624+5488C>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+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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 12 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAL	NM_182978.4	c.624+5488C>T		intron_variant	Intron 4 of 11	ENST00000334049.11	NP_892023.1
GNAL	NM_001369387.1	c.393+5488C>T		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+5488C>T		intron_variant	Intron 4 of 11	1	NM_182978.4	ENSP00000334051.5
GNAL	ENST00000423027.8	c.393+5488C>T		intron_variant	Intron 4 of 11	1	NM_001369387.1	ENSP00000408489.2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31595 AN: 152166 Hom.: 5451 Cov.: 33

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.: 33 AF XY: 0.202 AC XY: 15047 AN XY: 74478

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: 52 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7730 AN: 68010

Other (OTH) AF: 0.188 AC: 398 AN: 2114

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.94
DANN	Benign	0.19
PhyloP100		-0.21
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: rs9947295; hg19: chr18-11759432;