rs3738029

Variant names:

• chr1-154602845-G-A
• rs3738029
• NM_001111.5:c.16-219C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001365045.1(ADAR):​c.43-219C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,140 control chromosomes in the GnomAD database, including 6,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6360 hom., cov: 33)
• Consequence: ADAR NM_001365045.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.566
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-154602845-G-A is Benign according to our data. Variant chr1-154602845-G-A is described in ClinVar as Benign. ClinVar VariationId is 1275613.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 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_001111.5	MANE Select	c.16-219C>T		intron	N/A	NP_001102.3
	ADAR	NM_001365045.1		c.43-219C>T		intron	N/A	NP_001351974.1
	ADAR	NM_015840.4		c.16-219C>T		intron	N/A	NP_056655.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	ENST00000368474.9	TSL:1 MANE Select	c.16-219C>T		intron	N/A	ENSP00000357459.4
	ADAR	ENST00000368471.8	TSL:1	c.-870-219C>T		intron	N/A	ENSP00000357456.3
	ADAR	ENST00000649724.2		c.46-219C>T		intron	N/A	ENSP00000497932.2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43917 AN: 152022 Hom.: 6343 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.289 AC: 43970 AN: 152140 Hom.: 6360 Cov.: 33 AF XY: 0.287 AC XY: 21316 AN XY: 74364

African (AFR) AF: 0.284 AC: 11772 AN: 41516

American (AMR) AF: 0.239 AC: 3656 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 959 AN: 3472

East Asian (EAS) AF: 0.292 AC: 1505 AN: 5160

South Asian (SAS) AF: 0.229 AC: 1103 AN: 4820

European-Finnish (FIN) AF: 0.348 AC: 3680 AN: 10584

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20272 AN: 67974

Other (OTH) AF: 0.300 AC: 635 AN: 2114

Alfa AF: 0.288 Hom.: 854

Bravo AF: 0.280

Asia WGS AF: 0.280 AC: 972 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.26
PhyloP100		-0.57
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: rs3738029; hg19: chr1-154575321;