Genetic Variant GNAO1-DT:n.6C>T (chr16-56191113-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000662188.1(GNAO1-DT):n.6C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 149,266 control chromosomes in the GnomAD database, including 37,415 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 37407 hom., cov: 30)

Exomes 𝑓: 0.81 ( 8 hom. )

Consequence

GNAO1-DT
ENST00000662188.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.76

Publications

1 publications found

Variant links:

Genes affected

GNAO1-DT (HGNC:27543): (GNAO1 divergent transcript)

GNAO1-DT links:

GNAO1 (HGNC:4389): (G protein subunit alpha o1) The protein encoded by this gene represents the alpha subunit of the Go heterotrimeric G-protein signal-transducing complex. Defects in this gene are a cause of early-onset epileptic encephalopathy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

GNAO1 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 17
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
movement disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
neurodevelopmental disorder with involuntary movements
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

GNAO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAO1-DT	NR_027078.2 link	n.-19C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
GNAO1-DT	ENST00000662188.1 link	n.6C>T	non_coding_transcript_exon_variant	Exon 1 of 4
GNAO1-DT	ENST00000665141.2 link	n.47+450C>T	intron_variant	Intron 1 of 3
GNAO1	ENST00000714052.1 link	n.102-1145G>A	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.694

AC:

103536

AN:

149136

Hom.:

37407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.795

Gnomad AMR

AF:

0.710

Gnomad ASJ

AF:

0.781

Gnomad EAS

AF:

0.580

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.778

Gnomad MID

AF:

0.774

Gnomad NFE

AF:

0.809

Gnomad OTH

AF:

0.731

GnomAD4 exome

AF:

0.808

AC:

AN:

Hom.:

Cov.:

AF XY:

0.833

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.833

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.694

AC:

103553

AN:

149240

Hom.:

37407

Cov.:

AF XY:

0.691

AC XY:

50344

AN XY:

72842

show subpopulations

African (AFR)

AF:

0.494

AC:

20286

AN:

41076

American (AMR)

AF:

0.709

AC:

10676

AN:

15052

Ashkenazi Jewish (ASJ)

AF:

0.781

AC:

2679

AN:

3432

East Asian (EAS)

AF:

0.580

AC:

2864

AN:

4938

South Asian (SAS)

AF:

0.594

AC:

2848

AN:

4798

European-Finnish (FIN)

AF:

0.778

AC:

7570

AN:

9724

Middle Eastern (MID)

AF:

0.778

AC:

224

AN:

288

European-Non Finnish (NFE)

AF:

0.809

AC:

54175

AN:

66948

Other (OTH)

AF:

0.727

AC:

1511

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1455

2910

4365

5820

7275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.745

Hom.:

5285

Bravo

AF:

0.686

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 21, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

1.8

PromoterAI

-0.020

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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16-56191113-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over