rs899234

Positions:

• chr16-56320167-G-A
• chr16-56320167-G-C
• chr16-56320167-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.304-8464G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,092 control chromosomes in the GnomAD database, including 48,846 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 0.80 (48846 hom., cov: 31)
• Consequence: GNAO1 NM_020988.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAO1	NM_020988.3	c.304-8464G>A		intron_variant		ENST00000262493.12
GNAO1	NM_138736.3	c.304-8464G>A		intron_variant
GNAO1	XM_011523003.4	c.178-8464G>A		intron_variant
GNAO1	XR_007064866.1	n.1051-8464G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAO1	ENST00000262493.12	c.304-8464G>A		intron_variant		1	NM_020988.3	P1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121235 AN: 151974 Hom.: 48819 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.814

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.798 AC: 121316 AN: 152092 Hom.: 48846 Cov.: 31 AF XY: 0.800 AC XY: 59447 AN XY: 74334

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.815

Alfa AF: 0.827 Hom.: 53169

Bravo AF: 0.800

Asia WGS AF: 0.849 AC: 2953 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.28
DANN	Benign	0.44

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: rs899234; hg19: chr16-56354079;