rs1127317

chr1-154583564-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001111.5(ADAR):c.*1242A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,014 control chromosomes in the GnomAD database, including 6,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (6751 hom., cov: 32)
  • Exomes 𝑓: 0.40 (1 hom.)
• Consequence: ADAR NM_001111.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.48

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-154583564-T-G is Benign according to our data. Variant chr1-154583564-T-G is described in ClinVar as [Benign]. Clinvar id is 292726.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAR	NM_001111.5	c.*1242A>C		3_prime_UTR_variant	15/15	ENST00000368474.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAR	ENST00000368474.9	c.*1242A>C		3_prime_UTR_variant	15/15	1	NM_001111.5	P3

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45147 AN: 151886 Hom.: 6737 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.400 AC: 4 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.297 AC: 45198 AN: 152004 Hom.: 6751 Cov.: 32 AF XY: 0.295 AC XY: 21928 AN XY: 74314

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.306

Alfa AF: 0.293 Hom.: 1557

Bravo AF: 0.290

Asia WGS AF: 0.281 AC: 975 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Symmetrical dyschromatosis of extremities Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.091
Dann	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1127317; hg19: chr1-154556040;