rs1127317

Variant names:

• chr1-154583564-T-G
• rs1127317
• NM_001111.5:c.*1242A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365045.1(ADAR):​c.*1242A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,014 control chromosomes in the GnomAD database, including 6,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (6751 hom., cov: 32)
  • Exomes 𝑓: 0.40 (1 hom.)
• Consequence: ADAR NM_001365045.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.48
• Publications: 18 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-154583564-T-G is Benign according to our data. Variant chr1-154583564-T-G is described in ClinVar as Benign. ClinVar VariationId is 292726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 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.*1242A>C		3_prime_UTR	Exon 15 of 15	NP_001102.3
	ADAR	NM_001365045.1		c.*1242A>C		3_prime_UTR	Exon 15 of 15	NP_001351974.1
	ADAR	NM_015840.4		c.*1242A>C		3_prime_UTR	Exon 15 of 15	NP_056655.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	ENST00000368474.9	TSL:1 MANE Select	c.*1242A>C		3_prime_UTR	Exon 15 of 15	ENSP00000357459.4
	ADAR	ENST00000368471.8	TSL:1	c.*1242A>C		3_prime_UTR	Exon 15 of 15	ENSP00000357456.3
	ADAR	ENST00000649724.2		c.*1242A>C		3_prime_UTR	Exon 15 of 15	ENSP00000497932.2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45147 AN: 151886 Hom.: 6737 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.400 AC: 4 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.667 AC: 4 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.297 AC: 45198 AN: 152004 Hom.: 6751 Cov.: 32 AF XY: 0.295 AC XY: 21928 AN XY: 74314

African (AFR) AF: 0.315 AC: 13033 AN: 41414

American (AMR) AF: 0.241 AC: 3684 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3470

East Asian (EAS) AF: 0.293 AC: 1516 AN: 5170

South Asian (SAS) AF: 0.229 AC: 1106 AN: 4822

European-Finnish (FIN) AF: 0.348 AC: 3678 AN: 10570

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20214 AN: 67968

Other (OTH) AF: 0.306 AC: 646 AN: 2112

Alfa AF: 0.294 Hom.: 1608

Bravo AF: 0.290

Asia WGS AF: 0.281 AC: 975 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Symmetrical dyschromatosis of extremities (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.091
DANN	Benign	0.62
PhyloP100		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1127317; hg19: chr1-154556040;