rs1498374

chr1-85321651-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698

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 -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/exons	MANE	UniProt
DDAH1	NM_012137.4	c.742-83G>A		intron_variant		ENST00000284031.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDAH1	ENST00000284031.13	c.742-83G>A		intron_variant		1	NM_012137.4	P1
BCL10-AS1	ENST00000426125.1	n.67+43913C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22963 AN: 152082 Hom.: 2127 Cov.: 32

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

Gnomad4 AFR exome AF: 0.0364

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.151 AC: 22955 AN: 152200 Hom.: 2128 Cov.: 32 AF XY: 0.151 AC XY: 11262 AN XY: 74434

Gnomad4 AFR AF: 0.0407

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: 0.167

Alfa AF: 0.188 Hom.: 4704

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
Dann	Benign	0.23

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: rs1498374; hg19: chr1-85787334; COSMIC: COSV52303253;