Variant 1-154589449-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001111.5(ADAR):c.2682G>A(p.Val894=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,611,136 control chromosomes in the GnomAD database, including 68,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6515 hom., cov: 32)

Exomes 𝑓: 0.29 ( 61723 hom. )

Consequence

ADAR
NM_001111.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.386

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 1-154589449-C-T is Benign according to our data. Variant chr1-154589449-C-T is described in ClinVar as [Benign]. Clinvar id is 257474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154589449-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.386 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 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.2682G>A	p.Val894=	synonymous_variant	9/15	ENST00000368474.9	NP_001102.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000368474.9 linkuse as main transcript	c.2682G>A	p.Val894=	synonymous_variant	9/15	1	NM_001111.5	ENSP00000357459	P3	P55265-1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44293

AN:

151998

Hom.:

6504

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.271

AC:

68087

AN:

251046

Hom.:

9571

AF XY:

0.274

AC XY:

37217

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.280

Gnomad EAS exome

AF:

0.282

Gnomad SAS exome

AF:

0.239

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.292

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.288

AC:

420437

AN:

1459020

Hom.:

61723

Cov.:

AF XY:

0.286

AC XY:

207334

AN XY:

726010

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.175

Gnomad4 ASJ exome

AF:

0.283

Gnomad4 EAS exome

AF:

0.268

Gnomad4 SAS exome

AF:

0.233

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.295

Gnomad4 OTH exome

AF:

0.295

GnomAD4 genome

AF:

0.291

AC:

44337

AN:

152116

Hom.:

6515

Cov.:

AF XY:

0.289

AC XY:

21497

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.304

Gnomad4 AMR

AF:

0.240

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.287

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.291

Hom.:

8263

Bravo

AF:

0.284

Asia WGS

AF:

0.276

AC:

959

AN:

3478

EpiCase

AF:

0.291

EpiControl

AF:

0.297

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2018	This variant is associated with the following publications: (PMID: 31423758) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 12, 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

-0.38

CADD

Benign

9.5

DANN

Benign

0.76

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

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

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