Genetic Variant GNAO1-DT:n.1115T>C (chr16-56189980-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000501259.5(GNAO1-DT):n.1115T>C 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 0.454 in 151,992 control chromosomes in the GnomAD database, including 15,807 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 0.45 ( 15807 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

GNAO1-DT
ENST00000501259.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Publications

4 publications found

Variant links:

COSMIC-nc: COSV52613952

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
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:

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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=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000501259.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1-DT	NR_027078.2		n.1115T>C		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GNAO1-DT	ENST00000501259.5	TSL:1	n.1115T>C	non_coding_transcript_exon	Exon 1 of 5
GNAO1-DT	ENST00000569025.1	TSL:5	n.28T>C	non_coding_transcript_exon	Exon 1 of 2
GNAO1-DT	ENST00000662188.1		n.1139T>C	non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

68953

AN:

151874

Hom.:

15806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.582

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.455

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.454

AC:

68977

AN:

151992

Hom.:

15807

Cov.:

AF XY:

0.455

AC XY:

33828

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.410

AC:

17004

AN:

41436

American (AMR)

AF:

0.469

AC:

7174

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

1377

AN:

3468

East Asian (EAS)

AF:

0.581

AC:

3004

AN:

5166

South Asian (SAS)

AF:

0.386

AC:

1858

AN:

4810

European-Finnish (FIN)

AF:

0.516

AC:

5445

AN:

10546

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.463

AC:

31477

AN:

67962

Other (OTH)

AF:

0.455

AC:

962

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1915

3830

5746

7661

9576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.456

Hom.:

20633

Bravo

AF:

0.454

Asia WGS

AF:

0.427

AC:

1484

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.4

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over