rs2587891

Variant names:

• chr16-56335253-A-C
• rs2587891
• NM_020988.3:c.593+396A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-56335253-A-C
• chr16-56335253-A-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.593+396A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,178 control chromosomes in the GnomAD database, including 44,653 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 0.77 (44653 hom., cov: 33)
• Consequence: GNAO1 NM_020988.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.79
• Publications: 5 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAO1	NM_020988.3	c.593+396A>C		intron_variant	Intron 5 of 8	ENST00000262493.12	NP_066268.1
GNAO1	NM_138736.3	c.593+396A>C		intron_variant	Intron 5 of 7		NP_620073.2
GNAO1	XM_011523003.4	c.467+396A>C		intron_variant	Intron 5 of 8		XP_011521305.1
GNAO1	XR_007064866.1	n.1340+396A>C		intron_variant	Intron 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAO1	ENST00000262493.12	c.593+396A>C		intron_variant	Intron 5 of 8	1	NM_020988.3	ENSP00000262493.6

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116377 AN: 152060 Hom.: 44609 Cov.: 33

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.765 AC: 116474 AN: 152178 Hom.: 44653 Cov.: 33 AF XY: 0.770 AC XY: 57262 AN XY: 74412

African (AFR) AF: 0.754 AC: 31324 AN: 41524

American (AMR) AF: 0.747 AC: 11429 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2750 AN: 3472

East Asian (EAS) AF: 0.855 AC: 4412 AN: 5162

South Asian (SAS) AF: 0.800 AC: 3860 AN: 4826

European-Finnish (FIN) AF: 0.839 AC: 8902 AN: 10612

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51215 AN: 67974

Other (OTH) AF: 0.776 AC: 1638 AN: 2110

Alfa AF: 0.754 Hom.: 164589

Bravo AF: 0.758

Asia WGS AF: 0.850 AC: 2957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.061
DANN	Benign	0.43
PhyloP100		-6.8
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: rs2587891; hg19: chr16-56369165;