chr1-154604579-T-G

Position:

• chr1-154604579-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001111.5(ADAR):​c.16-1953A>C 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 152,154 control chromosomes in the GnomAD database, including 13,007 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 0.38 (13007 hom., cov: 32)
• Consequence: ADAR NM_001111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAR	NM_001111.5	c.16-1953A>C		intron_variant		ENST00000368474.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAR	ENST00000368474.9	c.16-1953A>C		intron_variant		1	NM_001111.5	P3

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58541 AN: 152036 Hom.: 13007 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.385 AC: 58539 AN: 152154 Hom.: 13007 Cov.: 32 AF XY: 0.387 AC XY: 28813 AN XY: 74362

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.393

Alfa AF: 0.349 Hom.: 1901

Bravo AF: 0.379

Asia WGS AF: 0.431 AC: 1501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0060
DANN	Benign	0.42

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: rs3766922; hg19: chr1-154577055;