dbSNP rs922445: GNAO1:c.304-20484G>A (chr16-56308147-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 NM_020988.3(GNAO1):c.304-20484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,142 control chromosomes in the GnomAD database, including 3,011 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 0.19 ( 3011 hom., cov: 32)

Exomes 𝑓: 0.23 ( 0 hom. )

Consequence

GNAO1
NM_020988.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0960

Publications

5 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: 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:

ENSG00000279764 (HGNC:):

ENSG00000279764 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
GNAO1	NM_020988.3 link	c.304-20484G>A	intron_variant	Intron 3 of 8	ENST00000262493.12	NP_066268.1
GNAO1	NM_138736.3 link	c.304-20484G>A	intron_variant	Intron 3 of 7		NP_620073.2
GNAO1	XM_011523003.4 link	c.178-20484G>A	intron_variant	Intron 3 of 8		XP_011521305.1
GNAO1	XR_007064866.1 link	n.1051-20484G>A	intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAO1	ENST00000262493.12 link	c.304-20484G>A		intron_variant	Intron 3 of 8	1	NM_020988.3	ENSP00000262493.6

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29050

AN:

151998

Hom.:

3008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.178

GnomAD4 exome

AF:

0.231

AC:

AN:

Hom.:

Cov.:

AF XY:

0.182

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.200

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.191

AC:

29073

AN:

152116

Hom.:

3011

Cov.:

AF XY:

0.194

AC XY:

14421

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.191

AC:

7931

AN:

41490

American (AMR)

AF:

0.261

AC:

3989

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

423

AN:

3472

East Asian (EAS)

AF:

0.425

AC:

2198

AN:

5166

South Asian (SAS)

AF:

0.119

AC:

574

AN:

4816

European-Finnish (FIN)

AF:

0.202

AC:

2140

AN:

10584

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.165

AC:

11239

AN:

67988

Other (OTH)

AF:

0.181

AC:

382

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1167

2334

3501

4668

5835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.174

Hom.:

5031

Bravo

AF:

0.194

Asia WGS

AF:

0.232

AC:

804

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.73

(source)

DANN

Benign

0.53

PhyloP100

-0.096

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over