rs17388568

Variant names:

• chr4-122408207-G-A
• rs17388568
• NM_139243.4:c.848+176G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 97 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139243.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAD1	NM_139243.4	MANE Select	c.848+176G>A		intron	N/A	NP_640336.1	Q96M93-1
	ADAD1	NM_001159285.2		c.848+176G>A		intron	N/A	NP_001152757.1	A0A140VKH5
	ADAD1	NM_001159295.2		c.794+176G>A		intron	N/A	NP_001152767.1	Q96M93-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAD1	ENST00000296513.7	TSL:2 MANE Select	c.848+176G>A		intron	N/A	ENSP00000296513.2	Q96M93-1
	ADAD1	ENST00000388724.6	TSL:1	c.848+176G>A		intron	N/A	ENSP00000373376.2	Q96M93-2
	ADAD1	ENST00000388725.2	TSL:2	c.794+176G>A		intron	N/A	ENSP00000373377.2	Q96M93-3

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

African (AFR) AF: 0.0566 AC: 2350 AN: 41528

American (AMR) AF: 0.154 AC: 2362 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3468

East Asian (EAS) AF: 0.129 AC: 671 AN: 5182

South Asian (SAS) AF: 0.135 AC: 653 AN: 4826

European-Finnish (FIN) AF: 0.413 AC: 4351 AN: 10542

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18867 AN: 67960

Other (OTH) AF: 0.191 AC: 404 AN: 2110

Alfa AF: 0.247 Hom.: 22277

Bravo AF: 0.175

Asia WGS AF: 0.111 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.5
DANN	Benign	0.64
PhyloP100		0.82
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17388568; hg19: chr4-123329362;