dbSNP rs2335230: ADAR:c.-871+10703T>G (chr1-154617152-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000368471.8(ADAR):c.-871+10703T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,128 control chromosomes in the GnomAD database, including 2,812 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2812 hom., cov: 32)

Consequence

ADAR
ENST00000368471.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.311

Publications

15 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
ADAR	NM_001365045.1 link	c.42+10802T>G	intron_variant	Intron 1 of 14	NP_001351974.1
ADAR	NM_001025107.3 link	c.-871+10703T>G	intron_variant	Intron 1 of 14	NP_001020278.1
ADAR	NM_001365046.1 link	c.-735+10802T>G	intron_variant	Intron 1 of 15	NP_001351975.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
ADAR	ENST00000368471.8 link	c.-871+10703T>G	intron_variant	Intron 1 of 14	1	ENSP00000357456.3
ADAR	ENST00000649724.2 link	c.45+10802T>G	intron_variant	Intron 1 of 14		ENSP00000497932.2
ADAR	ENST00000680270.2 link	c.45+10802T>G	intron_variant	Intron 1 of 15		ENSP00000505532.2

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27194

AN:

152012

Hom.:

2814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0841

Gnomad AMI

AF:

0.0835

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.198

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.179

AC:

27203

AN:

152128

Hom.:

2812

Cov.:

AF XY:

0.182

AC XY:

13512

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0840

AC:

3490

AN:

41528

American (AMR)

AF:

0.220

AC:

3361

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

708

AN:

3470

East Asian (EAS)

AF:

0.156

AC:

804

AN:

5166

South Asian (SAS)

AF:

0.333

AC:

1603

AN:

4810

European-Finnish (FIN)

AF:

0.211

AC:

2232

AN:

10568

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14440

AN:

67992

Other (OTH)

AF:

0.197

AC:

417

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1128

2255

3383

4510

5638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.202

Hom.:

14119

Bravo

AF:

0.174

Asia WGS

AF:

0.246

AC:

855

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.0

(source)

DANN

Benign

0.62

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over