rs3738032

chr1-154600943-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.122

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]

ACMG classification

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/exons	MANE	UniProt
ADAR	NM_001111.5	c.1601+98G>A		intron_variant		ENST00000368474.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAR	ENST00000368474.9	c.1601+98G>A		intron_variant		1	NM_001111.5	P3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33014 AN: 151772 Hom.: 3646 Cov.: 31

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.: 22 AF XY: 0.215 AC XY: 146810 AN XY: 683046

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.: 31 AF XY: 0.216 AC XY: 16019 AN XY: 74256

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 10, 2019

- -

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

Other links and lift over

dbSNP: rs3738032; hg19: chr1-154573419; COSMIC: COSV52716096; COSMIC: COSV52716096;