Variant 18-11689611-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_182978.4(GNAL):c.48G>A(p.Gly16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,347,028 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

GNAL
NM_182978.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0420

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 18-11689611-G-A is Benign according to our data. Variant chr18-11689611-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1112127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.042 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0014 (212/151968) while in subpopulation AFR AF= 0.00501 (208/41490). AF 95% confidence interval is 0.00446. There are 0 homozygotes in gnomad4. There are 96 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 212 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAL	NM_182978.4 linkuse as main transcript	c.48G>A	p.Gly16=	synonymous_variant	1/12	ENST00000334049.11
GNAL	XM_006722324.4 linkuse as main transcript	c.48G>A	p.Gly16=	synonymous_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAL	ENST00000334049.11 linkuse as main transcript	c.48G>A	p.Gly16=	synonymous_variant	1/12	1	NM_182978.4		P38405-2

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

213

AN:

151860

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000272

AC:

AN:

3672

Hom.:

AF XY:

0.00

AC XY:

AN XY:

2300

show subpopulations

Gnomad AFR exome

AF:

0.00962

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000150

AC:

179

AN:

1195060

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

581020

show subpopulations

Gnomad4 AFR exome

AF:

0.00638

Gnomad4 AMR exome

AF:

0.000532

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000213

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000403

Gnomad4 OTH exome

AF:

0.000389

GnomAD4 genome

AF:

0.00140

AC:

212

AN:

151968

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00501

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000854

Hom.:

Bravo

AF:

0.00142

Asia WGS

AF:

0.000882

AC:

AN:

3416

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dystonic disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.9

DANN

Benign

0.96

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over