rs9427094

Variant summary

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

The NM_001111.5(ADAR):c.3443+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,613,746 control chromosomes in the GnomAD database, including 182,154 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13975 hom., cov: 31)

Exomes 𝑓: 0.48 ( 168179 hom. )

Consequence

ADAR
NM_001111.5 splice_region, intron

Scores

Splicing: ADA: 0.0004036

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 1.78

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-154585209-C-T is Benign according to our data. Variant chr1-154585209-C-T is described in ClinVar as [Benign]. Clinvar id is 257475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154585209-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAR	NM_001111.5 linkuse as main transcript	c.3443+8G>A		splice_region_variant, intron_variant		ENST00000368474.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAR	ENST00000368474.9 linkuse as main transcript	c.3443+8G>A		splice_region_variant, intron_variant		1	NM_001111.5	P3	P55265-1

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62772

AN:

151788

Hom.:

13973

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.581

Gnomad AMR

AF:

0.476

Gnomad ASJ

AF:

0.498

Gnomad EAS

AF:

0.538

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.466

AC:

117123

AN:

251442

Hom.:

27966

AF XY:

0.464

AC XY:

63071

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.499

Gnomad EAS exome

AF:

0.535

Gnomad SAS exome

AF:

0.412

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.487

Gnomad OTH exome

AF:

0.467

GnomAD4 exome

AF:

0.477

AC:

697104

AN:

1461840

Hom.:

168179

Cov.:

AF XY:

0.476

AC XY:

346518

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.237

Gnomad4 AMR exome

AF:

0.517

Gnomad4 ASJ exome

AF:

0.488

Gnomad4 EAS exome

AF:

0.560

Gnomad4 SAS exome

AF:

0.415

Gnomad4 FIN exome

AF:

0.451

Gnomad4 NFE exome

AF:

0.487

Gnomad4 OTH exome

AF:

0.459

GnomAD4 genome

AF:

0.413

AC:

62776

AN:

151906

Hom.:

13975

Cov.:

AF XY:

0.414

AC XY:

30773

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.243

Gnomad4 AMR

AF:

0.476

Gnomad4 ASJ

AF:

0.498

Gnomad4 EAS

AF:

0.538

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.438

Gnomad4 NFE

AF:

0.483

Gnomad4 OTH

AF:

0.411

Alfa

AF:

0.449

Hom.:

7401

Bravo

AF:

0.412

Asia WGS

AF:

0.433

AC:

1506

AN:

3478

EpiCase

AF:

0.480

EpiControl

AF:

0.478

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 70% of patients studied by a panel of primary immunodeficiencies. Number of patients: 67. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Symmetrical dyschromatosis of extremities

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Aicardi-Goutieres syndrome 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Other:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

Cadd

Benign

8.3

Dann

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00040

dbscSNV1_RF

Benign

0.010

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

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