rs12125166

chr1-154609653-C-T

Variant summary

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

The ENST00000368471.8(ADAR):c.-870-7027G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,998 control chromosomes in the GnomAD database, including 13,853 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 0.41 (13853 hom., cov: 31)
• Consequence: ADAR ENST00000368471.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAR	NM_001025107.3	c.-870-7027G>A		intron_variant
ADAR	NM_001365045.1	c.43-7027G>A		intron_variant
ADAR	NM_001365046.1	c.-734-7027G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAR	ENST00000368471.8	c.-870-7027G>A		intron_variant		1
ADAR	ENST00000648311.1	c.-870-7027G>A		intron_variant
ADAR	ENST00000649022.2	c.-870-7027G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62676 AN: 151880 Hom.: 13852 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.412 AC: 62694 AN: 151998 Hom.: 13853 Cov.: 31 AF XY: 0.414 AC XY: 30752 AN XY: 74274

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.412

Alfa AF: 0.436 Hom.: 2545

Bravo AF: 0.409

Asia WGS AF: 0.433 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.2
Dann	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12125166; hg19: chr1-154582129;