rs10468679

Positions:

• chr18-11695677-C-T

Variant summary

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

The ENST00000334049.11(GNAL):​c.376+5738C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 152,096 control chromosomes in the GnomAD database, including 983 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 0.094 (983 hom., cov: 32)
• Consequence: GNAL ENST00000334049.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAL	NM_182978.4	c.376+5738C>T		intron_variant		ENST00000334049.11	NP_892023.1
GNAL	XM_006722324.4	c.376+5738C>T		intron_variant			XP_006722387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAL	ENST00000334049.11	c.376+5738C>T		intron_variant		1	NM_182978.4	ENSP00000334051
GNAL	ENST00000585590.1	n.250+5738C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14299 AN: 151978 Hom.: 982 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0585

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0803

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.0833

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

GnomAD4 genome AF: 0.0941 AC: 14319 AN: 152096 Hom.: 983 Cov.: 32 AF XY: 0.0927 AC XY: 6892 AN XY: 74352

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0583

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0803

Gnomad4 FIN AF: 0.0411

Gnomad4 NFE AF: 0.0593

Gnomad4 OTH AF: 0.0824

Alfa AF: 0.0646 Hom.: 391

Bravo AF: 0.0976

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10468679; hg19: chr18-11695676;