16-56335253-A-C

Position:

• chr16-56335253-A-C

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
GNAO1	NM_020988.3	c.593+396A>C		intron_variant		ENST00000262493.12	NP_066268.1
GNAO1	NM_138736.3	c.593+396A>C		intron_variant			NP_620073.2
GNAO1	XM_011523003.4	c.467+396A>C		intron_variant			XP_011521305.1
GNAO1	XR_007064866.1	n.1340+396A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAO1	ENST00000262493.12	c.593+396A>C		intron_variant		1	NM_020988.3	ENSP00000262493	P1

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

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.792

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.839

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.776

Alfa AF: 0.752 Hom.: 67165

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

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: rs2587891; hg19: chr16-56369165;