rs922445

chr16-56308147-G-Achr16-56308147-G-Cchr16-56308147-G-T

Variant summary

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

The NM_020988.3(GNAO1):c.304-20484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,142 control chromosomes in the GnomAD database, including 3,011 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 0.19 (3011 hom., cov: 32)
  • Exomes 𝑓: 0.23 (0 hom.)
• Consequence: GNAO1 NM_020988.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAO1	NM_020988.3	c.304-20484G>A		intron_variant		ENST00000262493.12
GNAO1	NM_138736.3	c.304-20484G>A		intron_variant
GNAO1	XM_011523003.4	c.178-20484G>A		intron_variant
GNAO1	XR_007064866.1	n.1051-20484G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAO1	ENST00000262493.12	c.304-20484G>A		intron_variant		1	NM_020988.3	P1
	ENST00000623118.1	n.1303G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29050 AN: 151998 Hom.: 3008 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.231 AC: 6 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.182 AC XY: 4 AN XY: 22

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.191 AC: 29073 AN: 152116 Hom.: 3011 Cov.: 32 AF XY: 0.194 AC XY: 14421 AN XY: 74370

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.181

Alfa AF: 0.166 Hom.: 1330

Bravo AF: 0.194

Asia WGS AF: 0.232 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.73
Dann	Benign	0.53

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: rs922445; hg19: chr16-56342059;