rs1241321

Positions:

• chr1-85462196-A-G

Variant summary

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

The NM_012137.4(DDAH1):​c.303+2547T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,000 control chromosomes in the GnomAD database, including 7,859 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 0.32 (7859 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDAH1	NM_012137.4	c.303+2547T>C		intron_variant		ENST00000284031.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDAH1	ENST00000284031.13	c.303+2547T>C		intron_variant		1	NM_012137.4	P1
DDAH1	ENST00000426972.8	c.-7+33970T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48726 AN: 151882 Hom.: 7843 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.283

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.321 AC: 48768 AN: 152000 Hom.: 7859 Cov.: 32 AF XY: 0.321 AC XY: 23842 AN XY: 74296

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.282

Alfa AF: 0.312 Hom.: 7735

Bravo AF: 0.318

Asia WGS AF: 0.368 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.51

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: rs1241321; hg19: chr1-85927879;