rs1127314

Variant names:

• chr1-154583790-G-A
• rs1127314
• NM_001111.5:c.*1016C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-154583790-G-A
• chr1-154583790-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001111.5(ADAR):​c.*1016C>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 0.604 in 152,104 control chromosomes in the GnomAD database, including 29,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (29819 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ADAR NM_001111.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.32
• Publications: 21 publications found

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 Gene-Disease associations (from GenCC):

• Aicardi-Goutieres syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• dyschromatosis symmetrica hereditaria

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Aicardi-Goutieres syndrome 6

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• familial infantile bilateral striatal necrosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-154583790-G-A is Benign according to our data. Variant chr1-154583790-G-A is described in ClinVar as Benign. ClinVar VariationId is 292729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAR	NM_001111.5	c.*1016C>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000368474.9	NP_001102.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000368474.9	c.*1016C>T		3_prime_UTR_variant	Exon 15 of 15	1	NM_001111.5	ENSP00000357459.4

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91877 AN: 151984 Hom.: 29810 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.604 AC: 91898 AN: 152102 Hom.: 29819 Cov.: 33 AF XY: 0.609 AC XY: 45275 AN XY: 74336

African (AFR) AF: 0.343 AC: 14214 AN: 41478

American (AMR) AF: 0.724 AC: 11083 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2540 AN: 3472

East Asian (EAS) AF: 0.705 AC: 3642 AN: 5166

South Asian (SAS) AF: 0.767 AC: 3693 AN: 4816

European-Finnish (FIN) AF: 0.652 AC: 6888 AN: 10564

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47713 AN: 67984

Other (OTH) AF: 0.623 AC: 1318 AN: 2116

Alfa AF: 0.677 Hom.: 60465

Bravo AF: 0.600

Asia WGS AF: 0.690 AC: 2400 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Symmetrical dyschromatosis of extremities Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	0.044
DANN	Benign	0.55
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1127314; hg19: chr1-154556266;