1-154591665-T-C

Variant names:

• chr1-154591665-T-C
• rs3766927
• NM_001111.5:c.2271-1256A>G

Variant summary

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

The NM_001111.5(ADAR):​c.2271-1256A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,206 control chromosomes in the GnomAD database, including 31,610 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31610 hom., cov: 33)
• Consequence: ADAR NM_001111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.747 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	NM_001111.5	MANE Select	c.2271-1256A>G		intron	N/A	NP_001102.3
	ADAR	NM_001365045.1		c.2298-1256A>G		intron	N/A	NP_001351974.1
	ADAR	NM_015840.4		c.2271-1256A>G		intron	N/A	NP_056655.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	ENST00000368474.9	TSL:1 MANE Select	c.2271-1256A>G		intron	N/A	ENSP00000357459.4
	ADAR	ENST00000368471.8	TSL:1	c.1386-1256A>G		intron	N/A	ENSP00000357456.3
	ADAR	ENST00000649724.2		c.2301-1256A>G		intron	N/A	ENSP00000497932.2

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96406 AN: 152088 Hom.: 31594 Cov.: 33

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.634 AC: 96450 AN: 152206 Hom.: 31610 Cov.: 33 AF XY: 0.638 AC XY: 47458 AN XY: 74400

African (AFR) AF: 0.448 AC: 18588 AN: 41510

American (AMR) AF: 0.733 AC: 11214 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2509 AN: 3470

East Asian (EAS) AF: 0.707 AC: 3666 AN: 5186

South Asian (SAS) AF: 0.767 AC: 3707 AN: 4830

European-Finnish (FIN) AF: 0.653 AC: 6909 AN: 10588

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47682 AN: 68004

Other (OTH) AF: 0.647 AC: 1366 AN: 2112

Alfa AF: 0.658 Hom.: 4401

Bravo AF: 0.631

Asia WGS AF: 0.698 AC: 2429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.75
PhyloP100		-0.43
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: rs3766927; hg19: chr1-154564141;