1-85350451-T-C

Variant names:

• chr1-85350451-T-C
• rs2230820
• NM_012137.4:c.561A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 14 publications found

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]

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012137.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	NM_012137.4	MANE Select	c.561A>G	p.Ala187Ala	synonymous	Exon 4 of 6	NP_036269.1
	DDAH1	NM_001330655.2		c.261A>G	p.Ala87Ala	synonymous	Exon 4 of 6	NP_001317584.1
	DDAH1	NM_001134445.2		c.252A>G	p.Ala84Ala	synonymous	Exon 5 of 7	NP_001127917.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	ENST00000284031.13	TSL:1 MANE Select	c.561A>G	p.Ala187Ala	synonymous	Exon 4 of 6	ENSP00000284031.8
	DDAH1	ENST00000426972.8	TSL:1	c.252A>G	p.Ala84Ala	synonymous	Exon 5 of 7	ENSP00000411189.4
	DDAH1	ENST00000633113.1	TSL:2	c.261A>G	p.Ala87Ala	synonymous	Exon 4 of 6	ENSP00000488725.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23095 AN: 152034 Hom.: 2143 Cov.: 32

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

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.: 32 AF XY: 0.188 AC XY: 136403 AN XY: 727084

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

GnomAD4 genome AF: 0.152 AC: 23087 AN: 152152 Hom.: 2144 Cov.: 32 AF XY: 0.152 AC XY: 11324 AN XY: 74376

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: 63 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13248 AN: 67996

Other (OTH) AF: 0.168 AC: 354 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.8
DANN	Benign	0.84
PhyloP100		-0.086
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: rs2230820; hg19: chr1-85816134; COSMIC: COSV52302027;