1-154601491-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001111.5(ADAR):c.1151A>G(p.Lys384Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 1,613,916 control chromosomes in the GnomAD database, including 390,071 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31054 hom., cov: 32)

Exomes 𝑓: 0.70 ( 359017 hom. )

Consequence

ADAR
NM_001111.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -0.324

Publications

73 publications found

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 Gene-Disease associations (from GenCC):

Aicardi-Goutieres syndrome
Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
dyschromatosis symmetrica hereditaria
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
Aicardi-Goutieres syndrome 6
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
familial infantile bilateral striatal necrosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ADAR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1812625E-6).

BP6

Variant 1-154601491-T-C is Benign according to our data. Variant chr1-154601491-T-C is described in ClinVar as Benign. ClinVar VariationId is 195112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAR	NM_001111.5 link	c.1151A>G	p.Lys384Arg	missense_variant	Exon 2 of 15	ENST00000368474.9	NP_001102.3	P55265-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000368474.9 link	c.1151A>G	p.Lys384Arg	missense_variant	Exon 2 of 15	1	NM_001111.5	ENSP00000357459.4		P55265-1

Frequencies

GnomAD3 genomes

AF:

0.626

AC:

95137

AN:

152016

Hom.:

31043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.664

Gnomad AMR

AF:

0.730

Gnomad ASJ

AF:

0.723

Gnomad EAS

AF:

0.706

Gnomad SAS

AF:

0.766

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.644

GnomAD2 exomes

AF:

0.703

AC:

176710

AN:

251442

AF XY:

0.705

show subpopulations

Gnomad AFR exome

AF:

0.410

Gnomad AMR exome

AF:

0.817

Gnomad ASJ exome

AF:

0.710

Gnomad EAS exome

AF:

0.711

Gnomad FIN exome

AF:

0.657

Gnomad NFE exome

AF:

0.703

Gnomad OTH exome

AF:

0.699

GnomAD4 exome

AF:

0.699

AC:

1021224

AN:

1461782

Hom.:

359017

Cov.:

AF XY:

0.702

AC XY:

510715

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.417

AC:

13949

AN:

33480

American (AMR)

AF:

0.806

AC:

36042

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.707

AC:

18473

AN:

26134

East Asian (EAS)

AF:

0.730

AC:

28967

AN:

39700

South Asian (SAS)

AF:

0.760

AC:

65555

AN:

86256

European-Finnish (FIN)

AF:

0.664

AC:

35408

AN:

53346

Middle Eastern (MID)

AF:

0.719

AC:

4147

AN:

5768

European-Non Finnish (NFE)

AF:

0.699

AC:

777599

AN:

1111980

Other (OTH)

AF:

0.680

AC:

41084

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

21478

42957

64435

85914

107392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19626

39252

58878

78504

98130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.626

AC:

95169

AN:

152134

Hom.:

31054

Cov.:

AF XY:

0.630

AC XY:

46865

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.420

AC:

17405

AN:

41468

American (AMR)

AF:

0.730

AC:

11167

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.723

AC:

2506

AN:

3466

East Asian (EAS)

AF:

0.706

AC:

3657

AN:

5182

South Asian (SAS)

AF:

0.768

AC:

3698

AN:

4818

European-Finnish (FIN)

AF:

0.652

AC:

6900

AN:

10586

Middle Eastern (MID)

AF:

0.697

AC:

205

AN:

294

European-Non Finnish (NFE)

AF:

0.701

AC:

47674

AN:

68002

Other (OTH)

AF:

0.638

AC:

1351

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1714

3428

5143

6857

8571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.683

Hom.:

173537

Bravo

AF:

0.623

TwinsUK

AF:

0.705

AC:

2614

ALSPAC

AF:

0.693

AC:

2669

ESP6500AA

AF:

0.429

AC:

1888

ESP6500EA

AF:

0.700

AC:

6018

ExAC

AF:

0.696

AC:

84446

Asia WGS

AF:

0.697

AC:

2425

AN:

3478

EpiCase

AF:

0.704

EpiControl

AF:

0.697

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 21, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 90% of patients studied by a panel of primary immunodeficiencies. Number of patients: 86. Only high quality variants are reported. -

not provided

Benign:2Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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. -

Aug 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25098560, 31423758) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Symmetrical dyschromatosis of extremities

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aicardi-Goutieres syndrome 6

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.18

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.28

T;.;T;.;.;.;.;.;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.42

.;.;T;.;.;.;.;.;T;T;T

MetaRNN

Benign

0.0000012

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.0

M;.;M;.;.;.;.;.;.;M;.

PhyloP100

-0.32

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.070

N;.;.;.;N;.;.;.;.;.;.

REVEL

Benign

0.012

Sift

Benign

0.38

T;.;.;.;T;.;.;.;.;.;.

Sift4G

Benign

0.65

T;.;.;.;T;.;.;.;.;.;.

Polyphen

0.0

B;.;B;.;.;.;.;.;.;B;.

Vest4

0.011

MPC

0.20

ClinPred

0.0030

GERP RS

-0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.017

gMVP

0.072

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over