rs188870525

Variant names:

• chr16-56191113-G-A
• rs188870525
• ENST00000662188.1:n.6C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000662188.1(GNAO1-DT):​n.6C>T 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 0.694 in 149,266 control chromosomes in the GnomAD database, including 37,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (37407 hom., cov: 30)
  • Exomes 𝑓: 0.81 (8 hom.)
• Consequence: GNAO1-DT ENST00000662188.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.76
• Publications: 1 publications found

Genes affected

GNAO1-DT (HGNC:27543): (GNAO1 divergent transcript)

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 16-56191113-G-A is Benign according to our data. Variant chr16-56191113-G-A is described in ClinVar as Benign. ClinVar VariationId is 1283647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000662188.1. 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.-19C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1-DT	ENST00000662188.1		n.6C>T		non_coding_transcript_exon	Exon 1 of 4
	GNAO1-DT	ENST00000665141.2		n.47+450C>T		intron	N/A
	GNAO1	ENST00000714052.1		n.102-1145G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.694 AC: 103536 AN: 149136 Hom.: 37407 Cov.: 30

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.731

GnomAD4 exome AF: 0.808 AC: 21 AN: 26 Hom.: 8 Cov.: 0 AF XY: 0.833 AC XY: 15 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.833 AC: 20 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.694 AC: 103553 AN: 149240 Hom.: 37407 Cov.: 30 AF XY: 0.691 AC XY: 50344 AN XY: 72842

African (AFR) AF: 0.494 AC: 20286 AN: 41076

American (AMR) AF: 0.709 AC: 10676 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2679 AN: 3432

East Asian (EAS) AF: 0.580 AC: 2864 AN: 4938

South Asian (SAS) AF: 0.594 AC: 2848 AN: 4798

European-Finnish (FIN) AF: 0.778 AC: 7570 AN: 9724

Middle Eastern (MID) AF: 0.778 AC: 224 AN: 288

European-Non Finnish (NFE) AF: 0.809 AC: 54175 AN: 66948

Other (OTH) AF: 0.727 AC: 1511 AN: 2078

Alfa AF: 0.745 Hom.: 5285

Bravo AF: 0.686

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		1.8
PromoterAI		-0.020	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs188870525; hg19: chr16-56225025;