rs2335230

Variant names:

• chr1-154617152-A-C
• rs2335230
• ENST00000368471.8:c.-871+10703T>G

Variant summary

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

The NM_001365045.1(ADAR):​c.42+10802T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,128 control chromosomes in the GnomAD database, including 2,812 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 0.18 (2812 hom., cov: 32)
• Consequence: ADAR NM_001365045.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311
• Publications: 15 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 6

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• dyschromatosis symmetrica hereditaria

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• ADAR-related type 1 interferonopathy

  Inheritance: AR, AD Classification: DEFINITIVE Submitted by: ClinGen
• Aicardi-Goutieres syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365045.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	NM_001365045.1		c.42+10802T>G		intron	N/A	NP_001351974.1
	ADAR	NM_001025107.3		c.-871+10703T>G		intron	N/A	NP_001020278.1	P55265-5
	ADAR	NM_001365046.1		c.-735+10802T>G		intron	N/A	NP_001351975.1	P55265-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	ENST00000368471.8	TSL:1	c.-871+10703T>G		intron	N/A	ENSP00000357456.3	P55265-5
	ADAR	ENST00000649724.2		c.45+10802T>G		intron	N/A	ENSP00000497932.2	A0AAG2TPY2
	ADAR	ENST00000680270.2		c.45+10802T>G		intron	N/A	ENSP00000505532.2	A0AAG2U5V6

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27194 AN: 152012 Hom.: 2814 Cov.: 32

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.179 AC: 27203 AN: 152128 Hom.: 2812 Cov.: 32 AF XY: 0.182 AC XY: 13512 AN XY: 74356

African (AFR) AF: 0.0840 AC: 3490 AN: 41528

American (AMR) AF: 0.220 AC: 3361 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3470

East Asian (EAS) AF: 0.156 AC: 804 AN: 5166

South Asian (SAS) AF: 0.333 AC: 1603 AN: 4810

European-Finnish (FIN) AF: 0.211 AC: 2232 AN: 10568

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14440 AN: 67992

Other (OTH) AF: 0.197 AC: 417 AN: 2116

Alfa AF: 0.202 Hom.: 14119

Bravo AF: 0.174

Asia WGS AF: 0.246 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.62
PhyloP100		0.31
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: rs2335230; hg19: chr1-154589628;