18-11689453-C-T

Position:

• chr18-11689453-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182978.4(GNAL):​c.-111C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 440,482 control chromosomes in the GnomAD database, including 5,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (3822 hom., cov: 33)
  • Exomes 𝑓: 0.087 (1608 hom.)
• Consequence: GNAL NM_182978.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.108

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 18-11689453-C-T is Benign according to our data. Variant chr18-11689453-C-T is described in ClinVar as [Benign]. Clinvar id is 1280122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAL	NM_182978.4	c.-111C>T		5_prime_UTR_variant	1/12	ENST00000334049.11	NP_892023.1
GNAL	XM_006722324.4	c.-111C>T		5_prime_UTR_variant	1/6		XP_006722387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAL	ENST00000334049	c.-111C>T		5_prime_UTR_variant	1/12	1	NM_182978.4	ENSP00000334051.5

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25630 AN: 151996 Hom.: 3804 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0965

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.0486

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0834

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.0867 AC: 25001 AN: 288378 Hom.: 1608 Cov.: 5 AF XY: 0.0860 AC XY: 12474 AN XY: 144988

Gnomad4 AFR exome AF: 0.410

Gnomad4 AMR exome AF: 0.0828

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0000984

Gnomad4 SAS exome AF: 0.0933

Gnomad4 FIN exome AF: 0.0551

Gnomad4 NFE exome AF: 0.0829

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.169 AC: 25691 AN: 152104 Hom.: 3822 Cov.: 33 AF XY: 0.165 AC XY: 12249 AN XY: 74372

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.0962

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.0989

Gnomad4 FIN AF: 0.0486

Gnomad4 NFE AF: 0.0834

Gnomad4 OTH AF: 0.147

Alfa AF: 0.135 Hom.: 291

Bravo AF: 0.179

Asia WGS AF: 0.0610 AC: 212 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61495657; hg19: chr18-11689452;