rs11264222

Positions:

• chr1-154581881-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000680270.2(ADAR):​c.*2925G>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 0.293 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 ENST00000680270.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000679899.1	c.*2925G>A		3_prime_UTR_variant	15/15			ENSP00000505996
ADAR	ENST00000680270.2	c.*2925G>A		3_prime_UTR_variant	16/16			ENSP00000505532	A2
ADAR	ENST00000681056.2	c.*2925G>A		3_prime_UTR_variant	15/15			ENSP00000506234	A2

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

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.307

Alfa AF: 0.294 Hom.: 13443

Bravo AF: 0.285

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11264222; hg19: chr1-154554357;