rs17388568

Positions:

• chr4-122408207-G-A

Variant summary

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

The NM_139243.4(ADAD1):​c.848+176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,122 control chromosomes in the GnomAD database, including 4,013 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 0.20 (4013 hom., cov: 32)
• Consequence: ADAD1 NM_139243.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.818

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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAD1	NM_139243.4	c.848+176G>A		intron_variant		ENST00000296513.7	NP_640336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAD1	ENST00000296513.7	c.848+176G>A		intron_variant		2	NM_139243.4	ENSP00000296513	P1
ADAD1	ENST00000388724.6	c.848+176G>A		intron_variant		1		ENSP00000373376
ADAD1	ENST00000388725.2	c.794+176G>A		intron_variant		2		ENSP00000373377

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30551 AN: 152004 Hom.: 4016 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.201 AC: 30540 AN: 152122 Hom.: 4013 Cov.: 32 AF XY: 0.203 AC XY: 15120 AN XY: 74352

Gnomad4 AFR AF: 0.0566

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.191

Alfa AF: 0.253 Hom.: 10457

Bravo AF: 0.175

Asia WGS AF: 0.111 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.5
DANN	Benign	0.64

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: rs17388568; hg19: chr4-123329362;