rs2131902

Variant names:

• chr1-154587122-T-C
• rs2131902
• NM_001111.5:c.3020-759A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-154587122-T-C
• chr1-154587122-T-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001111.5(ADAR):​c.3020-759A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,928 control chromosomes in the GnomAD database, including 12,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

• Frequency: Genomes: 𝑓 0.38 (12664 hom., cov: 32)
• Consequence: ADAR NM_001111.5 intron
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: -0.162
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 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.3020-759A>G		intron	N/A	NP_001102.3	P55265-1
	ADAR	NM_001365045.1		c.3047-759A>G		intron	N/A	NP_001351974.1
	ADAR	NM_015840.4		c.2942-759A>G		intron	N/A	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.3020-759A>G		intron	N/A	ENSP00000357459.4	P55265-1
	ADAR	ENST00000368471.8	TSL:1	c.2135-759A>G		intron	N/A	ENSP00000357456.3	P55265-5
	ADAR	ENST00000649724.2		c.3050-759A>G		intron	N/A	ENSP00000497932.2	A0AAG2TPY2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58391 AN: 151810 Hom.: 12636 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.360

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.385 AC: 58464 AN: 151928 Hom.: 12664 Cov.: 32 AF XY: 0.381 AC XY: 28259 AN XY: 74252

African (AFR) AF: 0.597 AC: 24732 AN: 41418

American (AMR) AF: 0.276 AC: 4210 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 937 AN: 3470

East Asian (EAS) AF: 0.310 AC: 1602 AN: 5174

South Asian (SAS) AF: 0.234 AC: 1125 AN: 4806

European-Finnish (FIN) AF: 0.349 AC: 3678 AN: 10550

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21010 AN: 67926

Other (OTH) AF: 0.365 AC: 771 AN: 2110

Alfa AF: 0.346 Hom.: 4543

Bravo AF: 0.389

Asia WGS AF: 0.309 AC: 1074 AN: 3478

ClinVar

ClinVar submissions

Significance: protective

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Colorectal cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.66
PhyloP100		-0.16
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: rs2131902; hg19: chr1-154559598;