rs2086346

Positions:

• chr4-122412516-A-G

Variant summary

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

The NM_139243.4(ADAD1):​c.1020-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,303,190 control chromosomes in the GnomAD database, including 62,400 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 0.25 (5674 hom., cov: 32)
  • Exomes 𝑓: 0.30 (56726 hom.)
• Consequence: ADAD1 NM_139243.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

Genes affected

ADAD1 (HGNC:30713): (adenosine deaminase domain containing 1) Predicted to enable double-stranded RNA adenosine deaminase activity; double-stranded RNA binding activity; and tRNA-specific adenosine deaminase activity. Predicted to be involved in RNA processing and adenosine to inosine editing. Predicted to act upstream of or within spermatid development. Predicted to be located in nucleus. Predicted to be active in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAD1	NM_139243.4	c.1020-64A>G		intron_variant		ENST00000296513.7	NP_640336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAD1	ENST00000296513.7	c.1020-64A>G		intron_variant		2	NM_139243.4	ENSP00000296513.2
ADAD1	ENST00000388724.6	c.987-64A>G		intron_variant		1		ENSP00000373376.2
ADAD1	ENST00000388725.2	c.966-64A>G		intron_variant		2		ENSP00000373377.2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37655 AN: 151952 Hom.: 5660 Cov.: 32

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.304 AC: 350003 AN: 1151120 Hom.: 56726 AF XY: 0.313 AC XY: 182629 AN XY: 583512

Gnomad4 AFR exome AF: 0.0678

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.421

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.497

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.248 AC: 37687 AN: 152070 Hom.: 5674 Cov.: 32 AF XY: 0.254 AC XY: 18863 AN XY: 74336

Gnomad4 AFR AF: 0.0724

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.301

Alfa AF: 0.285 Hom.: 1512

Bravo AF: 0.236

Asia WGS AF: 0.422 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.36

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: rs2086346; hg19: chr4-123333671; COSMIC: COSV56643907; COSMIC: COSV56643907;