rs2550298

Positions:

• chr16-56334057-C-T

Variant summary

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

The NM_020988.3(GNAO1):​c.465-672C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,226 control chromosomes in the GnomAD database, including 14,617 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 0.43 (14617 hom., cov: 35)
• Consequence: GNAO1 NM_020988.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669

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]

GNAO1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAO1	NM_020988.3	c.465-672C>T		intron_variant		ENST00000262493.12	NP_066268.1
GNAO1	NM_138736.3	c.465-672C>T		intron_variant			NP_620073.2
GNAO1	XM_011523003.4	c.339-672C>T		intron_variant			XP_011521305.1
GNAO1	XR_007064866.1	n.1212-672C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAO1	ENST00000262493.12	c.465-672C>T		intron_variant		1	NM_020988.3	ENSP00000262493.6

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65395 AN: 152108 Hom.: 14596 Cov.: 35

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.430 AC: 65463 AN: 152226 Hom.: 14617 Cov.: 35 AF XY: 0.438 AC XY: 32580 AN XY: 74428

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.445

Alfa AF: 0.416 Hom.: 2265

Bravo AF: 0.433

Asia WGS AF: 0.585 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.88

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: rs2550298; hg19: chr16-56367969;