rs1127311

Variant names:

• chr1-154584187-G-A
• rs1127311
• NM_001111.5:c.*619C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-154584187-G-A
• chr1-154584187-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.*619C>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 0.419 in 152,404 control chromosomes in the GnomAD database, including 14,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14253 hom., cov: 33)
  • Exomes 𝑓: 0.44 (36 hom.)
• Consequence: ADAR NM_001111.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.27
• Publications: 26 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=-0.83).
• BP6: Variant 1-154584187-G-A is Benign according to our data. Variant chr1-154584187-G-A is described in ClinVar as Benign. ClinVar VariationId is 292740.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.*619C>T		3_prime_UTR	Exon 15 of 15	NP_001102.3	P55265-1
	ADAR	NM_001365045.1		c.*619C>T		3_prime_UTR	Exon 15 of 15	NP_001351974.1
	ADAR	NM_015840.4		c.*619C>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.*619C>T		3_prime_UTR	Exon 15 of 15	ENSP00000357459.4	P55265-1
	ADAR	ENST00000368471.8	TSL:1	c.*619C>T		3_prime_UTR	Exon 15 of 15	ENSP00000357456.3	P55265-5
	ADAR	ENST00000649724.2		c.*619C>T		3_prime_UTR	Exon 15 of 15	ENSP00000497932.2	A0AAG2TPY2

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63681 AN: 151982 Hom.: 14252 Cov.: 33

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.444 AC: 135 AN: 304 Hom.: 36 Cov.: 0 AF XY: 0.463 AC XY: 76 AN XY: 164

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.375 AC: 12 AN: 32

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.167 AC: 3 AN: 18

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.474 AC: 110 AN: 232

Other (OTH) AF: 0.500 AC: 8 AN: 16

GnomAD4 genome AF: 0.419 AC: 63681 AN: 152100 Hom.: 14253 Cov.: 33 AF XY: 0.420 AC XY: 31218 AN XY: 74362

African (AFR) AF: 0.257 AC: 10659 AN: 41510

American (AMR) AF: 0.477 AC: 7292 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1735 AN: 3466

East Asian (EAS) AF: 0.553 AC: 2862 AN: 5174

South Asian (SAS) AF: 0.412 AC: 1988 AN: 4828

European-Finnish (FIN) AF: 0.439 AC: 4636 AN: 10550

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.485 AC: 32980 AN: 67972

Other (OTH) AF: 0.415 AC: 874 AN: 2108

Alfa AF: 0.466 Hom.: 21679

Bravo AF: 0.418

Asia WGS AF: 0.436 AC: 1519 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	-0.83
CADD	Benign	0.29
DANN	Benign	0.56
PhyloP100		-1.3
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: rs1127311; hg19: chr1-154556663;