1-154601491-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 3P and 20B. PM1PP2BP4_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. 13/20 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

1
17

Clinical Significance

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

Conservation

PhyloP100: -0.324
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

PM1
In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity DSRAD_HUMAN
PP2
Missense variant in the ADAR gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 16 curated pathogenic missense variants (we use a threshold of 10). The gene has 30 curated benign missense variants. Gene score misZ: 2.2714 (below the threshold of 3.09). Trascript score misZ: 3.4067 (above the threshold of 3.09). GenCC associations: The gene is linked to dyschromatosis symmetrica hereditaria, Aicardi-Goutieres syndrome, Aicardi-Goutieres syndrome 6, Leigh syndrome, familial infantile bilateral striatal necrosis.
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 id is 195112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154601491-T-C is described in Lovd as [Benign].
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
ADARNM_001111.5 linkc.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
ADARENST00000368474.9 linkc.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.:
32
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
GnomAD3 exomes
AF:
0.703
AC:
176710
AN:
251442
Hom.:
63170
AF XY:
0.705
AC XY:
95877
AN XY:
135900
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 SAS exome
AF:
0.754
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.:
78
AF XY:
0.702
AC XY:
510715
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.417
Gnomad4 AMR exome
AF:
0.806
Gnomad4 ASJ exome
AF:
0.707
Gnomad4 EAS exome
AF:
0.730
Gnomad4 SAS exome
AF:
0.760
Gnomad4 FIN exome
AF:
0.664
Gnomad4 NFE exome
AF:
0.699
Gnomad4 OTH exome
AF:
0.680
GnomAD4 genome
AF:
0.626
AC:
95169
AN:
152134
Hom.:
31054
Cov.:
32
AF XY:
0.630
AC XY:
46865
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.420
Gnomad4 AMR
AF:
0.730
Gnomad4 ASJ
AF:
0.723
Gnomad4 EAS
AF:
0.706
Gnomad4 SAS
AF:
0.768
Gnomad4 FIN
AF:
0.652
Gnomad4 NFE
AF:
0.701
Gnomad4 OTH
AF:
0.638
Alfa
AF:
0.690
Hom.:
95117
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
May 21, 2015
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
PreventionGenetics, part of Exact Sciences
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
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) -

-
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. -

-
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
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.18
DANN
Benign
0.94
DEOGEN2
Benign
0.28
T;.;T;.;.;.;.;.;.;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.13
N
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
T
MutationAssessor
Uncertain
2.0
M;.;M;.;.;.;.;.;.;M;.
PrimateAI
Benign
0.20
T
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
T
GERP RS
-0.81
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.017
gMVP
0.072

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.

Other links and lift over

dbSNP: rs2229857; hg19: chr1-154573967; API