rs7227421

chr18-11749199-A-G

Variant summary

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

The NM_182978.4(GNAL):c.377-3654A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 150,872 control chromosomes in the GnomAD database, including 610 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 0.070 (610 hom., cov: 32)
• Consequence: GNAL NM_182978.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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 = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAL	NM_182978.4	c.377-3654A>G		intron_variant		ENST00000334049.11
GNAL	XM_006722324.4	c.377-3654A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAL	ENST00000334049.11	c.377-3654A>G		intron_variant		1	NM_182978.4

Frequencies

GnomAD3 genomes AF: 0.0701 AC: 10568 AN: 150770 Hom.: 608 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.0508

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.0682

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0635

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

GnomAD4 genome AF: 0.0702 AC: 10589 AN: 150872 Hom.: 610 Cov.: 32 AF XY: 0.0685 AC XY: 5048 AN XY: 73660

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0494

Gnomad4 ASJ AF: 0.0257

Gnomad4 EAS AF: 0.0401

Gnomad4 SAS AF: 0.0507

Gnomad4 FIN AF: 0.0115

Gnomad4 NFE AF: 0.0352

Gnomad4 OTH AF: 0.0635

Alfa AF: 0.0406 Hom.: 273

Bravo AF: 0.0765

Asia WGS AF: 0.0520 AC: 182 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	0.83
Dann	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7227421; hg19: chr18-11749198;