rs12125166

Variant names:

• chr1-154609653-C-T
• rs12125166
• ENST00000368471.8:c.-870-7027G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.91).
• 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 rank	MANE	Protein	UniProt
ADAR	NM_001365045.1	c.43-7027G>A		intron_variant	Intron 1 of 14		NP_001351974.1
ADAR	NM_001025107.3	c.-870-7027G>A		intron_variant	Intron 1 of 14		NP_001020278.1
ADAR	NM_001365046.1	c.-734-7027G>A		intron_variant	Intron 1 of 15		NP_001351975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000368471.8	c.-870-7027G>A		intron_variant	Intron 1 of 14	1		ENSP00000357456.3
ADAR	ENST00000649724.2	c.46-7027G>A		intron_variant	Intron 1 of 14			ENSP00000497932.2
ADAR	ENST00000680270.2	c.46-7027G>A		intron_variant	Intron 1 of 15			ENSP00000505532.2

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

African (AFR) AF: 0.255 AC: 10578 AN: 41454

American (AMR) AF: 0.469 AC: 7155 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1729 AN: 3472

East Asian (EAS) AF: 0.537 AC: 2772 AN: 5164

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4818

European-Finnish (FIN) AF: 0.439 AC: 4636 AN: 10560

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.476 AC: 32319 AN: 67950

Other (OTH) AF: 0.412 AC: 871 AN: 2114

Alfa AF: 0.430 Hom.: 2565

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
PhyloP100		-0.039
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: rs12125166; hg19: chr1-154582129;