chr18-11800067-C-A

Position:

• chr18-11800067-C-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• 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/exons	MANE	Protein	UniProt
GNAL	NM_001369387.1	c.394-24851C>A		intron_variant		ENST00000423027.8	NP_001356316.1
GNAL	NM_182978.4	c.625-24851C>A		intron_variant		ENST00000334049.11	NP_892023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAL	ENST00000334049.11	c.625-24851C>A		intron_variant		1	NM_182978.4	ENSP00000334051
GNAL	ENST00000423027.8	c.394-24851C>A		intron_variant		1	NM_001369387.1	ENSP00000408489	P1

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

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.306

Alfa AF: 0.257 Hom.: 3104

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10468681; hg19: chr18-11800066;