rs1477941

Positions:

• chr18-11692441-C-G
• chr18-11692441-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GNAL	NM_182978.4	c.376+2502C>G		intron_variant		ENST00000334049.11
GNAL	XM_006722324.4	c.376+2502C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAL	ENST00000334049.11	c.376+2502C>G		intron_variant		1	NM_182978.4
GNAL	ENST00000585590.1	n.250+2502C>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0537

Gnomad4 NFE AF: 0.0903

Gnomad4 OTH AF: 0.189

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1477941; hg19: chr18-11692440;