ENST00000368471.8:c.-870-12567T>C

Variant names:

• chr1-154615193-A-G
• rs4845384
• ENST00000368471.8:c.-870-12567T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368471.8(ADAR):​c.-870-12567T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,960 control chromosomes in the GnomAD database, including 36,701 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36701 hom., cov: 31)
• Consequence: ADAR ENST00000368471.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368471.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	NM_001365045.1		c.43-12567T>C		intron	N/A	NP_001351974.1
	ADAR	NM_001025107.3		c.-870-12567T>C		intron	N/A	NP_001020278.1
	ADAR	NM_001365046.1		c.-734-12567T>C		intron	N/A	NP_001351975.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	ENST00000368471.8	TSL:1	c.-870-12567T>C		intron	N/A	ENSP00000357456.3
	ADAR	ENST00000649724.2		c.46-12567T>C		intron	N/A	ENSP00000497932.2
	ADAR	ENST00000680270.2		c.46-12567T>C		intron	N/A	ENSP00000505532.2

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105503 AN: 151842 Hom.: 36675 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.686

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.695 AC: 105568 AN: 151960 Hom.: 36701 Cov.: 31 AF XY: 0.696 AC XY: 51726 AN XY: 74268

African (AFR) AF: 0.690 AC: 28566 AN: 41404

American (AMR) AF: 0.748 AC: 11427 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2435 AN: 3468

East Asian (EAS) AF: 0.689 AC: 3563 AN: 5170

South Asian (SAS) AF: 0.750 AC: 3613 AN: 4816

European-Finnish (FIN) AF: 0.651 AC: 6865 AN: 10544

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46854 AN: 67970

Other (OTH) AF: 0.680 AC: 1434 AN: 2108

Alfa AF: 0.693 Hom.: 8394

Bravo AF: 0.701

Asia WGS AF: 0.707 AC: 2459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.58
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4845384; hg19: chr1-154587669;