rs10158674

Positions:

• chr1-85350451-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000284031.13(DDAH1):​c.561A>G​(p.Ala187=) 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 ENST00000284031.13 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.561A>G	p.Ala187=	synonymous_variant	4/6	ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.561A>G	p.Ala187=	synonymous_variant	4/6	1	NM_012137.4	ENSP00000284031	P1
BCL10-AS1	ENST00000426125.1	n.68-26315T>C		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.174 AC: 43588 AN: 251156 Hom.: 4128 AF XY: 0.172 AC XY: 23398 AN XY: 135718

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 SAS exome AF: 0.116

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

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.179

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

Gnomad4 AFR AF: 0.0435

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.168

Alfa AF: 0.175 Hom.: 1361

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
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs2230820; hg19: chr1-85816134; COSMIC: COSV52302027;