Genetic Variant NM_012137.4:c.742-83G>A (chr1-85321651-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_012137.4(DDAH1):c.742-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,056,364 control chromosomes in the GnomAD database, including 18,544 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 ( 2128 hom., cov: 32)

Exomes 𝑓: 0.19 ( 16416 hom. )

Consequence

DDAH1
NM_012137.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.698

Publications

9 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.742-83G>A		intron_variant	Intron 5 of 5	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.742-83G>A		intron_variant	Intron 5 of 5	1	NM_012137.4	ENSP00000284031.8		O94760-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22963

AN:

152082

Hom.:

2127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0409

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.170

GnomAD4 exome

AF:

0.187

AC:

169052

AN:

904164

Hom.:

16416

AF XY:

0.184

AC XY:

86484

AN XY:

469944

show subpopulations

African (AFR)

AF:

0.0364

AC:

808

AN:

22192

American (AMR)

AF:

0.211

AC:

8809

AN:

41744

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

3818

AN:

21380

East Asian (EAS)

AF:

0.104

AC:

3833

AN:

36828

South Asian (SAS)

AF:

0.118

AC:

8446

AN:

71724

European-Finnish (FIN)

AF:

0.226

AC:

11528

AN:

50928

Middle Eastern (MID)

AF:

0.145

AC:

667

AN:

4610

European-Non Finnish (NFE)

AF:

0.202

AC:

123728

AN:

613070

Other (OTH)

AF:

0.178

AC:

7415

AN:

41688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

6688

13375

20063

26750

33438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3172

6344

9516

12688

15860

<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:

0.151

AC:

22955

AN:

152200

Hom.:

2128

Cov.:

AF XY:

0.151

AC XY:

11262

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0407

AC:

1691

AN:

41550

American (AMR)

AF:

0.213

AC:

3252

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

638

AN:

3468

East Asian (EAS)

AF:

0.140

AC:

726

AN:

5168

South Asian (SAS)

AF:

0.110

AC:

531

AN:

4828

European-Finnish (FIN)

AF:

0.217

AC:

2295

AN:

10590

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13237

AN:

67984

Other (OTH)

AF:

0.167

AC:

352

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

998

1996

2993

3991

4989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<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:

0.177

Hom.:

7492

Bravo

AF:

0.147

Asia WGS

AF:

0.102

AC:

354

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.17

(source)

DANN

Benign

0.23

PhyloP100

-0.70

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over