rs876619

Variant names:

• chr16-56249622-C-A
• rs876619
• NM_020988.3:c.162-26309C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-56249622-C-A
• chr16-56249622-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020988.3(GNAO1):​c.162-26309C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,080 control chromosomes in the GnomAD database, including 1,606 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 0.13 (1606 hom., cov: 32)
• Consequence: GNAO1 NM_020988.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• Publications: 6 publications found

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)

ACMG classification

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 = 0.218 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.162-26309C>A		intron	N/A	NP_066268.1	P09471-1
	GNAO1	NM_138736.3		c.162-26309C>A		intron	N/A	NP_620073.2	P09471-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1	ENST00000262493.12	TSL:1 MANE Select	c.162-26309C>A		intron	N/A	ENSP00000262493.6	P09471-1
	GNAO1	ENST00000262494.13	TSL:1	c.162-26309C>A		intron	N/A	ENSP00000262494.7	P09471-2
	GNAO1	ENST00000638705.1	TSL:1	c.162-26309C>A		intron	N/A	ENSP00000491223.1	P09471-1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19604 AN: 151962 Hom.: 1604 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0778

Gnomad OTH AF: 0.0989

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19634 AN: 152080 Hom.: 1606 Cov.: 32 AF XY: 0.131 AC XY: 9757 AN XY: 74368

African (AFR) AF: 0.221 AC: 9174 AN: 41444

American (AMR) AF: 0.115 AC: 1755 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 306 AN: 3470

East Asian (EAS) AF: 0.116 AC: 599 AN: 5162

South Asian (SAS) AF: 0.200 AC: 962 AN: 4806

European-Finnish (FIN) AF: 0.117 AC: 1236 AN: 10608

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0778 AC: 5289 AN: 67990

Other (OTH) AF: 0.0993 AC: 210 AN: 2114

Alfa AF: 0.0840 Hom.: 401

Bravo AF: 0.128

Asia WGS AF: 0.169 AC: 587 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	1.7
DANN	Benign	0.59
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs876619; hg19: chr16-56283534;