dbSNP rs10158674: DDAH1:p.Ala187Ala (chr1-85350451-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_012137.4(DDAH1):c.561A>G(p.Ala187Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,613,702 control chromosomes in the GnomAD database, including 29,651 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 0.15 ( 2144 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27507 hom. )

Consequence

DDAH1
NM_012137.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0860

Publications

14 publications found

Variant links:

Genes affected

DDAH1 (HGNC:2715): (dimethylarginine dimethylaminohydrolase 1) This gene belongs to the dimethylarginine dimethylaminohydrolase (DDAH) gene family. The encoded enzyme plays a role in nitric oxide generation by regulating cellular concentrations of methylarginines, which in turn inhibit nitric oxide synthase activity. [provided by RefSeq, Jul 2008]

DDAH1 links:

BCL10-AS1 (HGNC:55868): (BCL10 antisense RNA 1)

BCL10-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP7

Synonymous conserved (PhyloP=-0.086 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4 link	c.561A>G	p.Ala187Ala	synonymous_variant	Exon 4 of 6	ENST00000284031.13	NP_036269.1	O94760-1B2R644

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13 link	c.561A>G	p.Ala187Ala	synonymous_variant	Exon 4 of 6	1	NM_012137.4	ENSP00000284031.8		O94760-1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23095

AN:

152034

Hom.:

2143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.171

GnomAD2 exomes

AF:

0.174

AC:

43588

AN:

251156

AF XY:

0.172

show subpopulations

Gnomad AFR exome

AF:

0.0399

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.182

Gnomad EAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.190

AC:

277520

AN:

1461550

Hom.:

27507

Cov.:

AF XY:

0.188

AC XY:

136403

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.0339

AC:

1135

AN:

33476

American (AMR)

AF:

0.209

AC:

9333

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

4599

AN:

26132

East Asian (EAS)

AF:

0.108

AC:

4272

AN:

39694

South Asian (SAS)

AF:

0.117

AC:

10091

AN:

86244

European-Finnish (FIN)

AF:

0.225

AC:

12002

AN:

53404

Middle Eastern (MID)

AF:

0.145

AC:

837

AN:

5758

European-Non Finnish (NFE)

AF:

0.202

AC:

224427

AN:

1111754

Other (OTH)

AF:

0.179

AC:

10824

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

11387

22774

34160

45547

56934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7810

15620

23430

31240

39050

<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:

0.152

AC:

23087

AN:

152152

Hom.:

2144

Cov.:

AF XY:

0.152

AC XY:

11324

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0435

AC:

1805

AN:

41534

American (AMR)

AF:

0.213

AC:

3259

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

639

AN:

3466

East Asian (EAS)

AF:

0.140

AC:

723

AN:

5168

South Asian (SAS)

AF:

0.110

AC:

531

AN:

4820

European-Finnish (FIN)

AF:

0.217

AC:

2293

AN:

10576

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13248

AN:

67996

Other (OTH)

AF:

0.168

AC:

354

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

956

1912

2868

3824

4780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<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:

0.173

Hom.:

1362

Bravo

AF:

0.149

Asia WGS

AF:

0.102

AC:

355

AN:

3476

EpiCase

AF:

0.195

EpiControl

AF:

0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.8

(source)

DANN

Benign

0.84

PhyloP100

-0.086

Mutation Taster

=99/1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over