rs2126986

chr16-56317795-A-Gchr16-56317795-A-T

Variant summary

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

The NM_020988.3(GNAO1):c.304-10836A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,858 control chromosomes in the GnomAD database, including 19,739 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 0.50 (19739 hom., cov: 31)
• Consequence: GNAO1 NM_020988.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAO1	NM_020988.3	c.304-10836A>G		intron_variant		ENST00000262493.12
GNAO1	NM_138736.3	c.304-10836A>G		intron_variant
GNAO1	XM_011523003.4	c.178-10836A>G		intron_variant
GNAO1	XR_007064866.1	n.1051-10836A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAO1	ENST00000262493.12	c.304-10836A>G		intron_variant		1	NM_020988.3	P1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75784 AN: 151740 Hom.: 19730 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.499 AC: 75826 AN: 151858 Hom.: 19739 Cov.: 31 AF XY: 0.490 AC XY: 36357 AN XY: 74170

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.484

Alfa AF: 0.473 Hom.: 29442

Bravo AF: 0.508

Asia WGS AF: 0.380 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.5
Dann	Benign	0.78

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: rs2126986; hg19: chr16-56351707;