Variant rs41289504 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_182978.4(GNAL):c.1245C>T(p.Ala415=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,614,020 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 12 hom., cov: 32)

Exomes 𝑓: 0.013 ( 138 hom. )

Consequence

GNAL
NM_182978.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.657

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 18-11881003-C-T is Benign according to our data. Variant chr18-11881003-C-T is described in ClinVar as [Benign]. Clinvar id is 416012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.657 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00805 (1226/152320) while in subpopulation NFE AF= 0.0132 (898/68028). AF 95% confidence interval is 0.0125. There are 12 homozygotes in gnomad4. There are 562 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1226 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAL	NM_182978.4 linkuse as main transcript	c.1245C>T	p.Ala415=	synonymous_variant	12/12	ENST00000334049.11
GNAL	NM_001369387.1 linkuse as main transcript	c.1014C>T	p.Ala338=	synonymous_variant	12/12	ENST00000423027.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAL	ENST00000334049.11 linkuse as main transcript	c.1245C>T	p.Ala415=	synonymous_variant	12/12	1	NM_182978.4		P38405-2
GNAL	ENST00000423027.8 linkuse as main transcript	c.1014C>T	p.Ala338=	synonymous_variant	12/12	1	NM_001369387.1	P1	P38405-1

Frequencies

GnomAD3 genomes

AF:

0.00805

AC:

1225

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00509

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00898

AC:

2253

AN:

250938

Hom.:

AF XY:

0.00911

AC XY:

1236

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00480

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00366

Gnomad FIN exome

AF:

0.00610

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0132

AC:

19269

AN:

1461700

Hom.:

138

Cov.:

AF XY:

0.0129

AC XY:

9353

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.00467

Gnomad4 ASJ exome

AF:

0.0126

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00399

Gnomad4 FIN exome

AF:

0.00631

Gnomad4 NFE exome

AF:

0.0156

Gnomad4 OTH exome

AF:

0.00952

GnomAD4 genome

AF:

0.00805

AC:

1226

AN:

152320

Hom.:

Cov.:

AF XY:

0.00754

AC XY:

562

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00509

Gnomad4 NFE

AF:

0.0132

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.00824

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0131

EpiControl

AF:

0.0155

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	GNAL: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 29, 2020	- -

Dystonic disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

1.5

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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