16-56189980-A-G

Variant names:

• chr16-56189980-A-G
• rs4784642
• ENST00000501259.5:n.1115T>C

Variant summary

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

The ENST00000501259.5(GNAO1-DT):​n.1115T>C 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 0.454 in 151,992 control chromosomes in the GnomAD database, including 15,807 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 0.45 (15807 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GNAO1-DT ENST00000501259.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 4 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: Orphanet, ClinGen
• movement disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina, ClinGen
• 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000501259.5. 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.1115T>C		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1-DT	ENST00000501259.5	TSL:1	n.1115T>C		non_coding_transcript_exon	Exon 1 of 5
	GNAO1-DT	ENST00000569025.1	TSL:5	n.28T>C		non_coding_transcript_exon	Exon 1 of 2
	GNAO1-DT	ENST00000662188.1		n.1139T>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68953 AN: 151874 Hom.: 15806 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.455

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.454 AC: 68977 AN: 151992 Hom.: 15807 Cov.: 32 AF XY: 0.455 AC XY: 33828 AN XY: 74286

African (AFR) AF: 0.410 AC: 17004 AN: 41436

American (AMR) AF: 0.469 AC: 7174 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3468

East Asian (EAS) AF: 0.581 AC: 3004 AN: 5166

South Asian (SAS) AF: 0.386 AC: 1858 AN: 4810

European-Finnish (FIN) AF: 0.516 AC: 5445 AN: 10546

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31477 AN: 67962

Other (OTH) AF: 0.455 AC: 962 AN: 2116

Alfa AF: 0.456 Hom.: 20633

Bravo AF: 0.454

Asia WGS AF: 0.427 AC: 1484 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		1.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4784642;

hg19: chr16-56223892;

COSMIC: COSV52613952;