rs2550298

Variant names:

• chr16-56334057-C-T
• rs2550298
• NM_020988.3:c.465-672C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 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: ClinGen, Orphanet
• movement disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020988.3. 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	NM_020988.3	MANE Select	c.465-672C>T		intron	N/A	NP_066268.1	P09471-1
	GNAO1	NM_138736.3		c.465-672C>T		intron	N/A	NP_620073.2	P09471-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAO1	ENST00000262493.12	TSL:1 MANE Select	c.465-672C>T		intron	N/A	ENSP00000262493.6	P09471-1
	GNAO1	ENST00000262494.13	TSL:1	c.465-672C>T		intron	N/A	ENSP00000262494.7	P09471-2
	GNAO1	ENST00000638705.1	TSL:1	c.465-672C>T		intron	N/A	ENSP00000491223.1	P09471-1

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

African (AFR) AF: 0.427 AC: 17719 AN: 41538

American (AMR) AF: 0.499 AC: 7632 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1396 AN: 3472

East Asian (EAS) AF: 0.752 AC: 3891 AN: 5172

South Asian (SAS) AF: 0.392 AC: 1891 AN: 4820

European-Finnish (FIN) AF: 0.489 AC: 5185 AN: 10606

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26356 AN: 67996

Other (OTH) AF: 0.445 AC: 941 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.88
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2550298; hg19: chr16-56367969;