18-11689670-CGGCCCT-C

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_118del(p.Leu38_Ala39del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,441,192 control chromosomes in the GnomAD database, including 95 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (61 hom., cov: 30)
  • Exomes 𝑓: 0.0014 (34 hom.)
• Consequence: GNAL NM_182978.4 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.255

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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_182978.4
• BP6: Variant 18-11689670-CGGCCCT-C is Benign according to our data. Variant chr18-11689670-CGGCCCT-C is described in ClinVar as [Benign]. Clinvar id is 1237593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-11689670-CGGCCCT-C is described in Lovd as [Likely_benign]. Variant chr18-11689670-CGGCCCT-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAL	NM_182978.4	c.113_118del	p.Leu38_Ala39del	inframe_deletion	1/12	ENST00000334049.11
GNAL	XM_006722324.4	c.113_118del	p.Leu38_Ala39del	inframe_deletion	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAL	ENST00000334049.11	c.113_118del	p.Leu38_Ala39del	inframe_deletion	1/12	1	NM_182978.4
GNAL	ENST00000585590.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2365 AN: 151818 Hom.: 61 Cov.: 30

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00649

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000295

Gnomad OTH AF: 0.0125

GnomAD3 exomes AF: 0.00104 AC: 65 AN: 62574 Hom.: 3 AF XY: 0.000681 AC XY: 25 AN XY: 36704

Gnomad AFR exome AF: 0.0478

Gnomad AMR exome AF: 0.00201

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000729

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000171

Gnomad OTH exome AF: 0.00173

GnomAD4 exome AF: 0.00138 AC: 1774 AN: 1289266 Hom.: 34 AF XY: 0.00117 AC XY: 741 AN XY: 634770

Gnomad4 AFR exome AF: 0.0520

Gnomad4 AMR exome AF: 0.00338

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000177

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000132

Gnomad4 OTH exome AF: 0.00362

GnomAD4 genome AF: 0.0156 AC: 2367 AN: 151926 Hom.: 61 Cov.: 30 AF XY: 0.0151 AC XY: 1125 AN XY: 74296

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.00648

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000295

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0000781 Hom.: 39

Bravo AF: 0.0185

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

Oct 31, 2018

- -

GNAL-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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;