rs116277860

Variant summary

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

The ENST00000262494.13(GNAO1):c.849G>A(p.Pro283=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,613,890 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 21 hom., cov: 33)

Exomes 𝑓: 0.00098 ( 28 hom. )

Consequence

GNAO1
ENST00000262494.13 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.443

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 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=-0.38).

BP6

Variant 16-56340959-G-A is Benign according to our data. Variant chr16-56340959-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 585944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.443 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00912 (1388/152270) while in subpopulation AFR AF= 0.0321 (1333/41552). AF 95% confidence interval is 0.0306. There are 21 homozygotes in gnomad4. There are 644 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd at 1387 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GNAO1	NM_020988.3 linkuse as main transcript	c.723+4099G>A		intron_variant		ENST00000262493.12
GNAO1	NM_138736.3 linkuse as main transcript	c.849G>A	p.Pro283=	synonymous_variant	7/8
GNAO1	XM_011523003.4 linkuse as main transcript	c.597+4099G>A		intron_variant
GNAO1	XR_007064866.1 linkuse as main transcript	n.1596G>A		non_coding_transcript_exon_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAO1	ENST00000262493.12 linkuse as main transcript	c.723+4099G>A		intron_variant		1	NM_020988.3	P1	P09471-1

Frequencies

GnomAD3 genomes

AF:

0.00912

AC:

1387

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00243

AC:

612

AN:

251386

Hom.:

AF XY:

0.00176

AC XY:

239

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.0338

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000976

AC:

1426

AN:

1461620

Hom.:

Cov.:

AF XY:

0.000822

AC XY:

598

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0347

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00912

AC:

1388

AN:

152270

Hom.:

Cov.:

AF XY:

0.00865

AC XY:

644

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0321

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00402

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 07, 2017	- -

GNAO1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 29, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Benign

0.61

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