rs9616

Variant names:

• chr1-154583257-A-T
• rs9616
• NM_001111.5:c.*1549T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-154583257-A-T
• chr1-154583257-A-G

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.*1549T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,268 control chromosomes in the GnomAD database, including 4,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4442 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: ADAR NM_001111.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.300
• Publications: 29 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=-0.85).
• BP6: Variant 1-154583257-A-T is Benign according to our data. Variant chr1-154583257-A-T is described in ClinVar as Benign. ClinVar VariationId is 292721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 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.*1549T>A		3_prime_UTR	Exon 15 of 15	NP_001102.3	P55265-1
	ADAR	NM_001365045.1		c.*1549T>A		3_prime_UTR	Exon 15 of 15	NP_001351974.1
	ADAR	NM_015840.4		c.*1549T>A		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.*1549T>A		3_prime_UTR	Exon 15 of 15	ENSP00000357459.4	P55265-1
	ADAR	ENST00000368471.8	TSL:1	c.*1549T>A		3_prime_UTR	Exon 15 of 15	ENSP00000357456.3	P55265-5
	ADAR	ENST00000649724.2		c.*1549T>A		3_prime_UTR	Exon 15 of 15	ENSP00000497932.2	A0AAG2TPY2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32913 AN: 152094 Hom.: 4440 Cov.: 32

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.214 AC: 12 AN: 56 Hom.: 1 Cov.: 0 AF XY: 0.225 AC XY: 9 AN XY: 40

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) AF: 0.100 AC: 3 AN: 30

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 9 AN: 24

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

GnomAD4 genome AF: 0.216 AC: 32913 AN: 152212 Hom.: 4442 Cov.: 32 AF XY: 0.215 AC XY: 15968 AN XY: 74408

African (AFR) AF: 0.0558 AC: 2319 AN: 41558

American (AMR) AF: 0.317 AC: 4848 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1722 AN: 5156

South Asian (SAS) AF: 0.167 AC: 806 AN: 4826

European-Finnish (FIN) AF: 0.197 AC: 2083 AN: 10584

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.284 AC: 19288 AN: 68006

Other (OTH) AF: 0.229 AC: 483 AN: 2106

Alfa AF: 0.237 Hom.: 620

Bravo AF: 0.223

Asia WGS AF: 0.190 AC: 665 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	-0.85
CADD	Benign	2.3
DANN	Benign	0.77
PhyloP100		-0.30
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: rs9616; hg19: chr1-154555733;