rs1127313

Variant names:

• chr1-154583949-G-A
• rs1127313
• NM_001111.5:c.*857C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-154583949-G-A
• chr1-154583949-G-T

Variant summary

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

The NM_001111.5(ADAR):​c.*857C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,102 control chromosomes in the GnomAD database, including 14,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14210 hom., cov: 33)
  • Exomes 𝑓: 0.50 (5 hom.)
• Consequence: ADAR NM_001111.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.102
• Publications: 31 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-154583949-G-A is Benign according to our data. Variant chr1-154583949-G-A is described in ClinVar as Benign. ClinVar VariationId is 292734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111.5. 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.*857C>T		3_prime_UTR	Exon 15 of 15	NP_001102.3	P55265-1
	ADAR	NM_001365045.1		c.*857C>T		3_prime_UTR	Exon 15 of 15	NP_001351974.1
	ADAR	NM_015840.4		c.*857C>T		3_prime_UTR	Exon 15 of 15	NP_056655.3	P55265-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	ENST00000368474.9	TSL:1 MANE Select	c.*857C>T		3_prime_UTR	Exon 15 of 15	ENSP00000357459.4	P55265-1
	ADAR	ENST00000368471.8	TSL:1	c.*857C>T		3_prime_UTR	Exon 15 of 15	ENSP00000357456.3	P55265-5
	ADAR	ENST00000649724.2		c.*857C>T		3_prime_UTR	Exon 15 of 15	ENSP00000497932.2	A0AAG2TPY2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63487 AN: 151948 Hom.: 14209 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.500 AC: 18 AN: 36 Hom.: 5 Cov.: 0 AF XY: 0.467 AC XY: 14 AN XY: 30

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

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: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.533 AC: 16 AN: 30

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.417 AC: 63487 AN: 152066 Hom.: 14210 Cov.: 33 AF XY: 0.419 AC XY: 31136 AN XY: 74362

African (AFR) AF: 0.253 AC: 10488 AN: 41484

American (AMR) AF: 0.476 AC: 7278 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1737 AN: 3472

East Asian (EAS) AF: 0.553 AC: 2863 AN: 5176

South Asian (SAS) AF: 0.411 AC: 1981 AN: 4820

European-Finnish (FIN) AF: 0.439 AC: 4648 AN: 10588

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32971 AN: 67928

Other (OTH) AF: 0.411 AC: 868 AN: 2110

Alfa AF: 0.462 Hom.: 22417

Bravo AF: 0.416

Asia WGS AF: 0.437 AC: 1520 AN: 3478

ClinVar

ClinVar submissions

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	-0.81
CADD	Benign	1.0
DANN	Benign	0.53
PhyloP100		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1127313; hg19: chr1-154556425;