rs11264222

Variant names:

• chr1-154581881-C-T
• rs11264222
• ENST00000647682.2:n.6591G>A

Variant summary

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

The ENST00000647682.2(ADAR):​n.6591G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,650 control chromosomes in the GnomAD database, including 6,526 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 0.29 (6526 hom., cov: 30)
• Consequence: ADAR ENST00000647682.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647682.2. 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_001111.5	MANE Select	c.*2925G>A		downstream_gene	N/A	NP_001102.3
	ADAR	NM_001365045.1		c.*2925G>A		downstream_gene	N/A	NP_001351974.1
	ADAR	NM_015840.4		c.*2925G>A		downstream_gene	N/A	NP_056655.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	ENST00000647682.2		n.6591G>A		non_coding_transcript_exon	Exon 14 of 14
	ADAR	ENST00000648714.2		n.*4081G>A		non_coding_transcript_exon	Exon 15 of 15	ENSP00000497434.2
	ADAR	ENST00000679375.1		n.*4838G>A		non_coding_transcript_exon	Exon 15 of 15	ENSP00000505887.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44360 AN: 151532 Hom.: 6510 Cov.: 30

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.293 AC: 44412 AN: 151650 Hom.: 6526 Cov.: 30 AF XY: 0.291 AC XY: 21542 AN XY: 74068

African (AFR) AF: 0.299 AC: 12342 AN: 41296

American (AMR) AF: 0.241 AC: 3680 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3470

East Asian (EAS) AF: 0.293 AC: 1503 AN: 5128

South Asian (SAS) AF: 0.227 AC: 1087 AN: 4786

European-Finnish (FIN) AF: 0.348 AC: 3659 AN: 10500

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20178 AN: 67920

Other (OTH) AF: 0.307 AC: 643 AN: 2094

Alfa AF: 0.293 Hom.: 20564

Bravo AF: 0.285

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.084
DANN	Benign	0.50
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs11264222; hg19: chr1-154554357;