ENST00000501259.5:n.-125C>A

Variant names:

• chr16-56191219-G-T
• rs537395792
• ENST00000501259.5:n.-125C>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000501259.5(GNAO1-DT):​n.-125C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 146,716 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (55 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNAO1-DT ENST00000501259.5 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.428

Genes affected

GNAO1-DT (HGNC:27543): (GNAO1 divergent transcript)

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-56191219-G-T is Benign according to our data. Variant chr16-56191219-G-T is described in ClinVar as [Benign]. Clinvar id is 1280694.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAO1-DT	NR_027078.2	n.-125C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAO1-DT	ENST00000501259.5	n.-125C>A		upstream_gene_variant		1
GNAO1-DT	ENST00000662188.1	n.-101C>A		upstream_gene_variant
GNAO1	ENST00000675160.1	n.-1017G>T		upstream_gene_variant				ENSP00000502403.1

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2479 AN: 146610 Hom.: 55 Cov.: 31

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00899

Gnomad ASJ AF: 0.00295

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.000653

Gnomad OTH AF: 0.0158

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0169 AC: 2486 AN: 146716 Hom.: 55 Cov.: 31 AF XY: 0.0164 AC XY: 1168 AN XY: 71436

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.00898

Gnomad4 ASJ AF: 0.00295

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000653

Gnomad4 OTH AF: 0.0157

Alfa AF: 0.000323 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.6
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs537395792; hg19: chr16-56225131;