rs4845384

Variant names:

• chr1-154615193-A-G
• rs4845384
• ENST00000368471.8:c.-870-12567T>C

Variant summary

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

The NM_001365045.1(ADAR):​c.43-12567T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,960 control chromosomes in the GnomAD database, including 36,701 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 0.69 (36701 hom., cov: 31)
• Consequence: ADAR NM_001365045.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAR	NM_001365045.1	c.43-12567T>C		intron_variant	Intron 1 of 14		NP_001351974.1
ADAR	NM_001025107.3	c.-870-12567T>C		intron_variant	Intron 1 of 14		NP_001020278.1
ADAR	NM_001365046.1	c.-734-12567T>C		intron_variant	Intron 1 of 15		NP_001351975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000368471.8	c.-870-12567T>C		intron_variant	Intron 1 of 14	1		ENSP00000357456.3
ADAR	ENST00000648311.1	c.-871+12243T>C		intron_variant	Intron 1 of 14			ENSP00000498137.1
ADAR	ENST00000649022.2	c.-871+9870T>C		intron_variant	Intron 2 of 15			ENSP00000496896.2

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105503 AN: 151842 Hom.: 36675 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.695 AC: 105568 AN: 151960 Hom.: 36701 Cov.: 31 AF XY: 0.696 AC XY: 51726 AN XY: 74268

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.680

Alfa AF: 0.699 Hom.: 4794

Bravo AF: 0.701

Asia WGS AF: 0.707 AC: 2459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4845384; hg19: chr1-154587669;