1-154583016-T-C

Variant names:

• chr1-154583016-T-C
• rs1127326
• NM_001111.5:c.*1790A>G

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.*1790A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,182 control chromosomes in the GnomAD database, including 29,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (29844 hom., cov: 32)
  • Exomes 𝑓: 0.88 (3 hom.)
• Consequence: ADAR NM_001365045.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.551
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-154583016-T-C is Benign according to our data. Variant chr1-154583016-T-C is described in ClinVar as Benign. ClinVar VariationId is 292717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.746 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.*1790A>G		3_prime_UTR	Exon 15 of 15	NP_001102.3
	ADAR	NM_001365045.1		c.*1790A>G		3_prime_UTR	Exon 15 of 15	NP_001351974.1
	ADAR	NM_015840.4		c.*1790A>G		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.*1790A>G		3_prime_UTR	Exon 15 of 15	ENSP00000357459.4
	ADAR	ENST00000368471.8	TSL:1	c.*1790A>G		3_prime_UTR	Exon 15 of 15	ENSP00000357456.3
	ADAR	ENST00000649724.2		c.*1790A>G		3_prime_UTR	Exon 15 of 15	ENSP00000497932.2

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91914 AN: 152056 Hom.: 29835 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.875 AC: 7 AN: 8 Hom.: 3 Cov.: 0 AF XY: 0.833 AC XY: 5 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) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.875 AC: 7 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.604 AC: 91935 AN: 152174 Hom.: 29844 Cov.: 32 AF XY: 0.609 AC XY: 45292 AN XY: 74392

African (AFR) AF: 0.342 AC: 14201 AN: 41490

American (AMR) AF: 0.725 AC: 11079 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2540 AN: 3472

East Asian (EAS) AF: 0.705 AC: 3648 AN: 5176

South Asian (SAS) AF: 0.767 AC: 3704 AN: 4832

European-Finnish (FIN) AF: 0.652 AC: 6896 AN: 10584

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.702 AC: 47741 AN: 68010

Other (OTH) AF: 0.623 AC: 1319 AN: 2116

Alfa AF: 0.628 Hom.: 4812

Bravo AF: 0.600

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	1.4
DANN	Benign	0.57
PhyloP100		0.55
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: rs1127326; hg19: chr1-154555492;