1-154591665-T-C

Position:

• chr1-154591665-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAR	NM_001111.5	c.2271-1256A>G		intron_variant		ENST00000368474.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAR	ENST00000368474.9	c.2271-1256A>G		intron_variant		1	NM_001111.5	P3

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

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.647

Alfa AF: 0.667 Hom.: 4330

Bravo AF: 0.631

Asia WGS AF: 0.698 AC: 2429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs3766927; hg19: chr1-154564141;