1-154583257-A-T

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.*1549T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,268 control chromosomes in the GnomAD database, including 4,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4442 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: ADAR NM_001111.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.300

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=-0.85).
• BP6: Variant 1-154583257-A-T is Benign according to our data. Variant chr1-154583257-A-T is described in ClinVar as [Benign]. Clinvar id is 292721.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAR	NM_001111.5	c.*1549T>A		3_prime_UTR_variant	15/15	ENST00000368474.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAR	ENST00000368474.9	c.*1549T>A		3_prime_UTR_variant	15/15	1	NM_001111.5	P3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32913 AN: 152094 Hom.: 4440 Cov.: 32

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.214 AC: 12 AN: 56 Hom.: 1 Cov.: 0 AF XY: 0.225 AC XY: 9 AN XY: 40

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.216 AC: 32913 AN: 152212 Hom.: 4442 Cov.: 32 AF XY: 0.215 AC XY: 15968 AN XY: 74408

Gnomad4 AFR AF: 0.0558

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.229

Alfa AF: 0.237 Hom.: 620

Bravo AF: 0.223

Asia WGS AF: 0.190 AC: 665 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	-0.85
Cadd	Benign	2.3
Dann	Benign	0.77

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: rs9616; hg19: chr1-154555733;