rs2161961

Positions:

• chr18-11774501-A-G
• chr18-11774501-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182978.4(GNAL):​c.624+20556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,116 control chromosomes in the GnomAD database, including 8,959 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 0.31 (8959 hom., cov: 33)
• Consequence: GNAL NM_182978.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAL	NM_001369387.1	c.393+20556A>G		intron_variant		ENST00000423027.8
GNAL	NM_182978.4	c.624+20556A>G		intron_variant		ENST00000334049.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAL	ENST00000334049.11	c.624+20556A>G		intron_variant		1	NM_182978.4
GNAL	ENST00000423027.8	c.393+20556A>G		intron_variant		1	NM_001369387.1	P1
	ENST00000666417.1	n.356+10735T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47147 AN: 151998 Hom.: 8942 Cov.: 33

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.310 AC: 47203 AN: 152116 Hom.: 8959 Cov.: 33 AF XY: 0.308 AC XY: 22886 AN XY: 74352

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.292

Alfa AF: 0.257 Hom.: 894

Bravo AF: 0.322

Asia WGS AF: 0.268 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.88
DANN	Benign	0.49

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: rs2161961; hg19: chr18-11774500;