rs899228

Positions:

• chr16-56353376-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020988.3(GNAO1):​c.878-1490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,154 control chromosomes in the GnomAD database, including 8,233 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 0.30 (8231 hom., cov: 33)
  • Exomes 𝑓: 0.23 (2 hom.)
• Consequence: GNAO1 NM_020988.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAO1	NM_020988.3	c.878-1490T>C		intron_variant		ENST00000262493.12
GNAO1	XM_011523003.4	c.752-1490T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAO1	ENST00000262493.12	c.878-1490T>C		intron_variant		1	NM_020988.3	P1
	ENST00000606772.1	n.149A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45586 AN: 151974 Hom.: 8219 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.226 AC: 14 AN: 62 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 13 AN XY: 52

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.300 AC: 45636 AN: 152092 Hom.: 8231 Cov.: 33 AF XY: 0.298 AC XY: 22157 AN XY: 74348

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.274

Alfa AF: 0.245 Hom.: 3078

Bravo AF: 0.316

Asia WGS AF: 0.414 AC: 1438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.53
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs899228; hg19: chr16-56387288;