18-11689670-C-CGGCCCT

Position:

• chr18-11689670-C-CGGCCCT

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_182978.4(GNAL):​c.113_118dupTGGCCC​(p.Leu38_Ala39dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,440,082 control chromosomes in the GnomAD database, including 16,271 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1561 hom., cov: 30)
  • Exomes 𝑓: 0.15 (14710 hom.)
• Consequence: GNAL NM_182978.4 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.750

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]

GNAL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_182978.4
• BP6: Variant 18-11689670-C-CGGCCCT is Benign according to our data. Variant chr18-11689670-C-CGGCCCT is described in ClinVar as [Benign]. Clinvar id is 1169619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAL	NM_182978.4	c.113_118dupTGGCCC	p.Leu38_Ala39dup	disruptive_inframe_insertion	1/12	ENST00000334049.11	NP_892023.1
GNAL	XM_006722324.4	c.113_118dupTGGCCC	p.Leu38_Ala39dup	disruptive_inframe_insertion	1/6		XP_006722387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAL	ENST00000334049.11	c.113_118dupTGGCCC	p.Leu38_Ala39dup	disruptive_inframe_insertion	1/12	1	NM_182978.4	ENSP00000334051.5
GNAL	ENST00000585590.1	n.-20_-19insGGCCCT		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21159 AN: 151802 Hom.: 1561 Cov.: 30

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0209

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.0842 AC: 5269 AN: 62574 Hom.: 337 AF XY: 0.0857 AC XY: 3146 AN XY: 36704

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.0407

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.00412

Gnomad SAS exome AF: 0.0607

Gnomad FIN exome AF: 0.0895

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.0844

GnomAD4 exome AF: 0.146 AC: 188021 AN: 1288172 Hom.: 14710 Cov.: 31 AF XY: 0.144 AC XY: 91635 AN XY: 634178

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.0781

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.0319

Gnomad4 SAS exome AF: 0.0855

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.139 AC: 21162 AN: 151910 Hom.: 1561 Cov.: 30 AF XY: 0.136 AC XY: 10099 AN XY: 74286

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.0210

Gnomad4 SAS AF: 0.0810

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.155

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 13, 2019

- -

Dystonic disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201898548; hg19: chr18-11689669;