chr1-154602344-T-C

Position:

chr1-154602344-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_001111.5(ADAR):c.298A>G(p.Arg100Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,609,886 control chromosomes in the GnomAD database, including 803,673 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R100A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 1.0 ( 75598 hom., cov: 32)

Exomes 𝑓: 1.0 ( 728075 hom. )

Consequence

ADAR
NM_001111.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.23

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ADAR. . Gene score misZ 2.2714 (greater than the threshold 3.09). Trascript score misZ 3.4067 (greater than threshold 3.09). GenCC has associacion of gene with 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=1.1511453E-6).

BP6

Variant 1-154602344-T-C is Benign according to our data. Variant chr1-154602344-T-C is described in ClinVar as [Benign]. Clinvar id is 500335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 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.298A>G	p.Arg100Gly	missense_variant	2/15	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.298A>G	p.Arg100Gly	missense_variant	2/15	1	NM_001111.5	ENSP00000357459.4		P55265-1

Frequencies

GnomAD3 genomes

AF:

0.996

AC:

151639

AN:

152204

Hom.:

75542

Cov.:

show subpopulations

Gnomad AFR

AF:

0.987

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.998

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.996

GnomAD3 exomes

AF:

0.999

AC:

247457

AN:

247740

Hom.:

123590

AF XY:

0.999

AC XY:

133835

AN XY:

133956

show subpopulations

Gnomad AFR exome

AF:

0.985

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1456845

AN:

1457564

Hom.:

728075

Cov.:

AF XY:

1.00

AC XY:

724735

AN XY:

725054

show subpopulations

Gnomad4 AFR exome

AF:

0.983

Gnomad4 AMR exome

AF:

0.999

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.999

GnomAD4 genome

AF:

0.996

AC:

151755

AN:

152322

Hom.:

75598

Cov.:

AF XY:

0.996

AC XY:

74206

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.987

Gnomad4 AMR

AF:

0.998

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.996

Alfa

AF:

0.999

Hom.:

117534

Bravo

AF:

0.995

TwinsUK

AF:

1.00

AC:

3707

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.988

AC:

4351

ESP6500EA

AF:

1.00

AC:

8599

ExAC

AF:

0.999

AC:

121246

Asia WGS

AF:

1.00

AC:

3477

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

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 02, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 96. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 07, 2017	- -

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

Benign:2

Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 08, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Aicardi-Goutieres syndrome 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Symmetrical dyschromatosis of extremities

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.27

DANN

Benign

0.11

DEOGEN2

Benign

0.23

T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.32

.;T;T

MetaRNN

Benign

0.0000012

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.17

N;.;.

REVEL

Benign

0.0080

Sift

Benign

0.81

T;.;.

Sift4G

Benign

0.41

T;.;.

Polyphen

0.0

B;B;B

Vest4

0.011

MPC

0.31

ClinPred

0.00041

GERP RS

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.058

gMVP

0.29

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