rs8053370

Positions:

• chr16-56228994-T-C

Variant summary

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

The NM_020988.3(GNAO1):​c.161+36378T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,242 control chromosomes in the GnomAD database, including 2,015 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 0.14 (2015 hom., cov: 33)
• Consequence: GNAO1 NM_020988.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAO1	NM_020988.3	c.161+36378T>C		intron_variant		ENST00000262493.12	NP_066268.1
GNAO1	NM_138736.3	c.161+36378T>C		intron_variant			NP_620073.2
GNAO1	XM_011523003.4	c.-337-6019T>C		intron_variant			XP_011521305.1
GNAO1	XR_007064866.1	n.908+36378T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAO1	ENST00000262493.12	c.161+36378T>C		intron_variant		1	NM_020988.3	ENSP00000262493	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21425 AN: 152124 Hom.: 2012 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0881

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0779

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.141 AC: 21457 AN: 152242 Hom.: 2015 Cov.: 33 AF XY: 0.143 AC XY: 10630 AN XY: 74448

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0881

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0779

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0975 Hom.: 443

Bravo AF: 0.142

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.90
DANN	Benign	0.34

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: rs8053370; hg19: chr16-56262906;