rs113827322

Variant names:

• chr16-56191124-G-A
• rs113827322
• ENST00000665141.2:n.47+439C>T

Variant summary

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

The ENST00000665141.2(GNAO1-DT):​n.47+439C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 149,136 control chromosomes in the GnomAD database, including 553 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (553 hom., cov: 31)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: GNAO1-DT ENST00000665141.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0580
• Publications: 2 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=-0.76).
• BP6: Variant 16-56191124-G-A is Benign according to our data. Variant chr16-56191124-G-A is described in ClinVar as Benign. ClinVar VariationId is 1238856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000665141.2. 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.-30C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1-DT	ENST00000665141.2		n.47+439C>T		intron	N/A
	GNAO1	ENST00000714052.1		n.102-1134G>A		intron	N/A
	GNAO1-DT	ENST00000715694.1		n.1976+1419C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12219 AN: 149002 Hom.: 552 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.0342

Gnomad SAS AF: 0.0937

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0321

Gnomad NFE AF: 0.0754

Gnomad OTH AF: 0.0586

GnomAD4 exome AF: 0.0714 AC: 2 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.0455 AC XY: 1 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

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: 0.0909 AC: 2 AN: 22

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0820 AC: 12231 AN: 149108 Hom.: 553 Cov.: 31 AF XY: 0.0825 AC XY: 6006 AN XY: 72782

African (AFR) AF: 0.106 AC: 4373 AN: 41148

American (AMR) AF: 0.0506 AC: 760 AN: 15032

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 158 AN: 3428

East Asian (EAS) AF: 0.0342 AC: 171 AN: 5006

South Asian (SAS) AF: 0.0940 AC: 452 AN: 4806

European-Finnish (FIN) AF: 0.110 AC: 1063 AN: 9652

Middle Eastern (MID) AF: 0.0276 AC: 8 AN: 290

European-Non Finnish (NFE) AF: 0.0754 AC: 5036 AN: 66766

Other (OTH) AF: 0.0580 AC: 120 AN: 2070

Alfa AF: 0.0792 Hom.: 77

Bravo AF: 0.0755

Asia WGS AF: 0.0730 AC: 247 AN: 3378

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	-0.76
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		-0.058
PromoterAI		-0.067	Neutral

Splicing

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

Other links and lift over

dbSNP: rs113827322; hg19: chr16-56225036;