dbSNP rs2086346: ADAD1:c.1020-64A>G (chr4-122412516-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.47

Publications

14 publications found

Variant links:

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]

ADAD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADAD1	NM_139243.4	MANE Select	c.1020-64A>G	intron	N/A	NP_640336.1
ADAD1	NM_001159285.2		c.987-64A>G	intron	N/A	NP_001152757.1
ADAD1	NM_001159295.2		c.966-64A>G	intron	N/A	NP_001152767.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADAD1	ENST00000296513.7	TSL:2 MANE Select	c.1020-64A>G	intron	N/A	ENSP00000296513.2
ADAD1	ENST00000388724.6	TSL:1	c.987-64A>G	intron	N/A	ENSP00000373376.2
ADAD1	ENST00000388725.2	TSL:2	c.966-64A>G	intron	N/A	ENSP00000373377.2

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37655

AN:

151952

Hom.:

5660

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0678

AC:

1852

AN:

27314

American (AMR)

AF:

0.301

AC:

12244

AN:

40628

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

9187

AN:

21816

East Asian (EAS)

AF:

0.333

AC:

12722

AN:

38182

South Asian (SAS)

AF:

0.497

AC:

36023

AN:

72488

European-Finnish (FIN)

AF:

0.296

AC:

13206

AN:

44572

Middle Eastern (MID)

AF:

0.469

AC:

2086

AN:

4452

European-Non Finnish (NFE)

AF:

0.289

AC:

246495

AN:

851750

Other (OTH)

AF:

0.324

AC:

16188

AN:

49918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

11743

23485

35228

46970

58713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7384

14768

22152

29536

36920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.248

AC:

37687

AN:

152070

Hom.:

5674

Cov.:

AF XY:

0.254

AC XY:

18863

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0724

AC:

3008

AN:

41534

American (AMR)

AF:

0.299

AC:

4566

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

1475

AN:

3466

East Asian (EAS)

AF:

0.339

AC:

1750

AN:

5166

South Asian (SAS)

AF:

0.505

AC:

2435

AN:

4822

European-Finnish (FIN)

AF:

0.293

AC:

3094

AN:

10576

Middle Eastern (MID)

AF:

0.517

AC:

150

AN:

290

European-Non Finnish (NFE)

AF:

0.298

AC:

20261

AN:

67922

Other (OTH)

AF:

0.301

AC:

637

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1369

2737

4106

5474

6843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.275

Hom.:

1650

Bravo

AF:

0.236

Asia WGS

AF:

0.422

AC:

1469

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.5

(source)

DANN

Benign

0.36

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over