Genetic Variant ADAR:c.1601+98G>A (chr1-154600943-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001111.5(ADAR):c.1601+98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,515,114 control chromosomes in the GnomAD database, including 36,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3655 hom., cov: 31)

Exomes 𝑓: 0.22 ( 33055 hom. )

Consequence

ADAR
NM_001111.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.122

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-154600943-C-T is Benign according to our data. Variant chr1-154600943-C-T is described in ClinVar as [Benign]. Clinvar id is 1259173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAR	NM_001111.5 link	c.1601+98G>A		intron_variant	Intron 2 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.1601+98G>A		intron_variant	Intron 2 of 14	1	NM_001111.5	ENSP00000357459.4		P55265-1

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33014

AN:

151772

Hom.:

3646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.216

AC:

294910

AN:

1363224

Hom.:

33055

Cov.:

AF XY:

0.215

AC XY:

146810

AN XY:

683046

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.268

Gnomad4 NFE exome

AF:

0.223

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.218

AC:

33050

AN:

151890

Hom.:

3655

Cov.:

AF XY:

0.216

AC XY:

16019

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.187

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.175

Gnomad4 FIN

AF:

0.277

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.225

Alfa

AF:

0.220

Hom.:

7149

Bravo

AF:

0.210

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

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 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.92

DANN

Benign

0.60

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