16-56192624-C-T

Variant names:

• chr16-56192624-C-T
• rs145872570
• NM_020988.3:c.161+8C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_020988.3(GNAO1):​c.161+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,550,386 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (16 hom., cov: 26)
  • Exomes 𝑓: 0.00062 (9 hom.)
• Consequence: GNAO1 NM_020988.3 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.668
• Publications: 0 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-DT (HGNC:27543): (GNAO1 divergent transcript)

GNAO1-AS1 (HGNC:24498): (GNAO1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 16-56192624-C-T is Benign according to our data. Variant chr16-56192624-C-T is described in ClinVar as Benign. ClinVar VariationId is 415873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0067 (1015/151470) while in subpopulation AFR AF = 0.0233 (959/41200). AF 95% confidence interval is 0.0221. There are 16 homozygotes in GnomAd4. There are 459 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1015 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAO1	NM_020988.3	c.161+8C>T		splice_region_variant, intron_variant	Intron 2 of 8	ENST00000262493.12	NP_066268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAO1	ENST00000262493.12	c.161+8C>T		splice_region_variant, intron_variant	Intron 2 of 8	1	NM_020988.3	ENSP00000262493.6

Frequencies

GnomAD3 genomes AF: 0.00669 AC: 1013 AN: 151354 Hom.: 16 Cov.: 26

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00177 AC: 445 AN: 251442 AF XY: 0.00124

Gnomad AFR exome AF: 0.0244

Gnomad AMR exome AF: 0.000954

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000703

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000620 AC: 867 AN: 1398916 Hom.: 9 Cov.: 26 AF XY: 0.000572 AC XY: 400 AN XY: 699526

African (AFR) AF: 0.0223 AC: 716 AN: 32164

American (AMR) AF: 0.00110 AC: 49 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25730

East Asian (EAS) AF: 0.00 AC: 0 AN: 39410

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.000353 AC: 2 AN: 5660

European-Non Finnish (NFE) AF: 0.0000180 AC: 19 AN: 1054566

Other (OTH) AF: 0.00136 AC: 79 AN: 58278

GnomAD4 genome AF: 0.00670 AC: 1015 AN: 151470 Hom.: 16 Cov.: 26 AF XY: 0.00621 AC XY: 459 AN XY: 73970

African (AFR) AF: 0.0233 AC: 959 AN: 41200

American (AMR) AF: 0.00263 AC: 40 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67906

Other (OTH) AF: 0.00522 AC: 11 AN: 2108

Alfa AF: 0.00195 Hom.: 3

Bravo AF: 0.00782

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Developmental and epileptic encephalopathy Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GNAO1-related disorder Benign:1

Apr 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		0.67
PromoterAI		-0.0031	Neutral
Mutation Taster		=100/0	polymorphism

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: rs145872570; hg19: chr16-56226536;