rs1127313

Positions:

• chr1-154583949-G-A
• chr1-154583949-G-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.*857C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,102 control chromosomes in the GnomAD database, including 14,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14210 hom., cov: 33)
  • Exomes 𝑓: 0.50 (5 hom.)
• Consequence: ADAR NM_001111.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.102

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=-0.81).
• BP6: Variant 1-154583949-G-A is Benign according to our data. Variant chr1-154583949-G-A is described in ClinVar as [Benign]. Clinvar id is 292734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAR	NM_001111.5	c.*857C>T		3_prime_UTR_variant	15/15	ENST00000368474.9	NP_001102.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000368474.9	c.*857C>T		3_prime_UTR_variant	15/15	1	NM_001111.5	ENSP00000357459	P3

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63487 AN: 151948 Hom.: 14209 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.500 AC: 18 AN: 36 Hom.: 5 Cov.: 0 AF XY: 0.467 AC XY: 14 AN XY: 30

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 NFE exome AF: 0.533

GnomAD4 genome AF: 0.417 AC: 63487 AN: 152066 Hom.: 14210 Cov.: 33 AF XY: 0.419 AC XY: 31136 AN XY: 74362

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.411

Alfa AF: 0.469 Hom.: 17688

Bravo AF: 0.416

Asia WGS AF: 0.437 AC: 1520 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Symmetrical dyschromatosis of extremities Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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	-0.81
CADD	Benign	1.0
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1127313; hg19: chr1-154556425;