Variant rs58655370 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001111.5(ADAR):c.15+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,608,580 control chromosomes in the GnomAD database, including 44,515 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6676 hom., cov: 33)

Exomes 𝑓: 0.22 ( 37839 hom. )

Consequence

ADAR
NM_001111.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: -0.176

Variant links:

Genes affected

ADAR (HGNC:225): (adenosine deaminase RNA specific) This gene encodes the enzyme responsible for RNA editing by site-specific deamination of adenosines. This enzyme destabilizes double-stranded RNA through conversion of adenosine to inosine. Mutations in this gene have been associated with dyschromatosis symmetrica hereditaria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

ADAR links:

ADAR (HGNC:):

ADAR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-154607982-C-A is Benign according to our data. Variant chr1-154607982-C-A is described in ClinVar as [Benign]. Clinvar id is 193166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154607982-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAR	NM_001111.5 linkuse as main transcript	c.15+10G>T		intron_variant		ENST00000368474.9	NP_001102.3	P55265-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000368474.9 linkuse as main transcript	c.15+10G>T		intron_variant		1	NM_001111.5	ENSP00000357459.4		P55265-1

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42326

AN:

152078

Hom.:

6666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.277

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.268

GnomAD3 exomes

AF:

0.242

AC:

56824

AN:

235084

Hom.:

7421

AF XY:

0.240

AC XY:

30814

AN XY:

128564

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.139

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.222

AC:

323172

AN:

1456384

Hom.:

37839

Cov.:

AF XY:

0.224

AC XY:

162368

AN XY:

724128

show subpopulations

Gnomad4 AFR exome

AF:

0.428

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.322

Gnomad4 FIN exome

AF:

0.209

Gnomad4 NFE exome

AF:

0.208

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.278

AC:

42376

AN:

152196

Hom.:

6676

Cov.:

AF XY:

0.278

AC XY:

20726

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.424

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.338

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.220

Hom.:

1258

Bravo

AF:

0.288

Asia WGS

AF:

0.268

AC:

933

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 46% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 22, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Aicardi-Goutieres syndrome 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Symmetrical dyschromatosis of extremities;C3539013:Aicardi-Goutieres syndrome 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Symmetrical dyschromatosis of extremities

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

8.9

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over