chr1-154585209-C-T

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.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:7O:1

Conservation

PhyloP100: 1.78

Publications

16 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 (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 VariationId is 257475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ADAR	NM_001111.5 link	c.3443+8G>A		splice_region_variant, intron_variant	Intron 14 of 14	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.3443+8G>A		splice_region_variant, intron_variant	Intron 14 of 14	1	NM_001111.5	ENSP00000357459.4		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

GnomAD2 exomes

AF:

0.466

AC:

117123

AN:

251442

AF XY:

0.464

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 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

African (AFR)

AF:

0.237

AC:

7939

AN:

33480

American (AMR)

AF:

0.517

AC:

23108

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

12757

AN:

26136

East Asian (EAS)

AF:

0.560

AC:

22243

AN:

39698

South Asian (SAS)

AF:

0.415

AC:

35759

AN:

86248

European-Finnish (FIN)

AF:

0.451

AC:

24090

AN:

53416

Middle Eastern (MID)

AF:

0.424

AC:

2447

AN:

5768

European-Non Finnish (NFE)

AF:

0.487

AC:

541062

AN:

1111978

Other (OTH)

AF:

0.459

AC:

27699

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

24526

49052

73579

98105

122631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15856

31712

47568

63424

79280

<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:

0.413

AC:

62776

AN:

151906

Hom.:

13975

Cov.:

AF XY:

0.414

AC XY:

30773

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.243

AC:

10065

AN:

41422

American (AMR)

AF:

0.476

AC:

7263

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

1728

AN:

3470

East Asian (EAS)

AF:

0.538

AC:

2769

AN:

5148

South Asian (SAS)

AF:

0.411

AC:

1973

AN:

4804

European-Finnish (FIN)

AF:

0.438

AC:

4620

AN:

10536

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.483

AC:

32835

AN:

67946

Other (OTH)

AF:

0.411

AC:

866

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1778

3556

5335

7113

8891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.449

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:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 70% of patients studied by a panel of primary immunodeficiencies. Number of patients: 67. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not provided

Benign:1Other: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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.3

(source)

DANN

Benign

0.51

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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