Genetic Variant NM_020988.3:c.878-1490T>C (chr16-56353376-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_020988.3(GNAO1):c.878-1490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,154 control chromosomes in the GnomAD database, including 8,233 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 0.30 ( 8231 hom., cov: 33)

Exomes 𝑓: 0.23 ( 2 hom. )

Consequence

GNAO1
NM_020988.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.987

Publications

8 publications found

Variant links:

Genes affected

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:

ENSG00000272372 (HGNC:):

ENSG00000272372 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020988.3. 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	NM_020988.3	MANE Select	c.878-1490T>C		intron	N/A	NP_066268.1	P09471-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GNAO1	ENST00000262493.12	TSL:1 MANE Select	c.878-1490T>C	intron	N/A	ENSP00000262493.6	P09471-1
GNAO1	ENST00000638705.1	TSL:1	c.878-1490T>C	intron	N/A	ENSP00000491223.1	P09471-1
GNAO1	ENST00000873096.1		c.902-1490T>C	intron	N/A	ENSP00000543155.1

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45586

AN:

151974

Hom.:

8219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.398

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.270

GnomAD4 exome

AF:

0.226

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.205

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.300

AC:

45636

AN:

152092

Hom.:

8231

Cov.:

AF XY:

0.298

AC XY:

22157

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.491

AC:

20334

AN:

41450

American (AMR)

AF:

0.250

AC:

3827

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

859

AN:

3470

East Asian (EAS)

AF:

0.398

AC:

2046

AN:

5146

South Asian (SAS)

AF:

0.372

AC:

1795

AN:

4824

European-Finnish (FIN)

AF:

0.144

AC:

1526

AN:

10608

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14358

AN:

67986

Other (OTH)

AF:

0.274

AC:

578

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1567

3133

4700

6266

7833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.255

Hom.:

12001

Bravo

AF:

0.316

Asia WGS

AF:

0.414

AC:

1438

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.53

(source)

DANN

Benign

0.62

PhyloP100

-0.99

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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