1-154599752-C-T

Variant names:

• chr1-154599752-C-T
• rs903323
• NM_001111.5:c.1602-1167G>A

Variant summary

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

The NM_001111.5(ADAR):​c.1602-1167G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,162 control chromosomes in the GnomAD database, including 12,944 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 0.38 (12944 hom., cov: 33)
• Consequence: ADAR NM_001111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.892
• Publications: 8 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAR	NM_001111.5	c.1602-1167G>A		intron_variant	Intron 2 of 14	ENST00000368474.9	NP_001102.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000368474.9	c.1602-1167G>A		intron_variant	Intron 2 of 14	1	NM_001111.5	ENSP00000357459.4

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58346 AN: 152044 Hom.: 12944 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.383 AC: 58345 AN: 152162 Hom.: 12944 Cov.: 33 AF XY: 0.386 AC XY: 28708 AN XY: 74390

African (AFR) AF: 0.153 AC: 6353 AN: 41526

American (AMR) AF: 0.461 AC: 7053 AN: 15294

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

East Asian (EAS) AF: 0.541 AC: 2798 AN: 5174

South Asian (SAS) AF: 0.411 AC: 1984 AN: 4828

European-Finnish (FIN) AF: 0.440 AC: 4644 AN: 10566

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32310 AN: 67988

Other (OTH) AF: 0.391 AC: 824 AN: 2110

Alfa AF: 0.436 Hom.: 6250

Bravo AF: 0.378

Asia WGS AF: 0.427 AC: 1485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.0
DANN	Benign	0.71
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs903323; hg19: chr1-154572228;