rs9427100

Variant names:

• chr1-154611286-G-A
• rs9427100
• ENST00000368471.8:c.-870-8660C>T

Variant summary

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

The NM_001365045.1(ADAR):​c.43-8660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,964 control chromosomes in the GnomAD database, including 13,504 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 0.40 (13504 hom., cov: 31)
• Consequence: ADAR NM_001365045.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 5 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 6

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• dyschromatosis symmetrica hereditaria

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• ADAR-related type 1 interferonopathy

  Inheritance: AR, AD Classification: DEFINITIVE Submitted by: ClinGen
• Aicardi-Goutieres syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365045.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	NM_001365045.1		c.43-8660C>T		intron	N/A	NP_001351974.1
	ADAR	NM_001025107.3		c.-870-8660C>T		intron	N/A	NP_001020278.1	P55265-5
	ADAR	NM_001365046.1		c.-734-8660C>T		intron	N/A	NP_001351975.1	P55265-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	ENST00000368471.8	TSL:1	c.-870-8660C>T		intron	N/A	ENSP00000357456.3	P55265-5
	ADAR	ENST00000649724.2		c.46-8660C>T		intron	N/A	ENSP00000497932.2	A0AAG2TPY2
	ADAR	ENST00000680270.2		c.46-8660C>T		intron	N/A	ENSP00000505532.2	A0AAG2U5V6

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61311 AN: 151850 Hom.: 13505 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.404 AC: 61325 AN: 151964 Hom.: 13504 Cov.: 31 AF XY: 0.405 AC XY: 30109 AN XY: 74276

African (AFR) AF: 0.225 AC: 9305 AN: 41442

American (AMR) AF: 0.466 AC: 7107 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1729 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2780 AN: 5172

South Asian (SAS) AF: 0.411 AC: 1982 AN: 4824

European-Finnish (FIN) AF: 0.439 AC: 4628 AN: 10538

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.475 AC: 32280 AN: 67936

Other (OTH) AF: 0.408 AC: 863 AN: 2114

Alfa AF: 0.436 Hom.: 5518

Bravo AF: 0.399

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.43
PhyloP100		-0.13
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: rs9427100; hg19: chr1-154583762;