rs1403951

Variant names:

• chr1-85474566-C-A
• rs1403951
• ENST00000426972.8:c.-7+21600G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134445.2(DDAH1):​c.-7+21600G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,924 control chromosomes in the GnomAD database, including 18,536 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 0.49 (18536 hom., cov: 31)
• Consequence: DDAH1 NM_001134445.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134445.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	NM_001134445.2		c.-7+21600G>T		intron	N/A	NP_001127917.1	O94760-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	ENST00000426972.8	TSL:1	c.-7+21600G>T		intron	N/A	ENSP00000411189.4	O94760-2

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75101 AN: 151806 Hom.: 18525 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.495 AC: 75151 AN: 151924 Hom.: 18536 Cov.: 31 AF XY: 0.494 AC XY: 36685 AN XY: 74250

African (AFR) AF: 0.515 AC: 21302 AN: 41398

American (AMR) AF: 0.490 AC: 7484 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1893 AN: 3466

East Asian (EAS) AF: 0.352 AC: 1817 AN: 5168

South Asian (SAS) AF: 0.559 AC: 2691 AN: 4812

European-Finnish (FIN) AF: 0.475 AC: 5002 AN: 10538

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33289 AN: 67952

Other (OTH) AF: 0.491 AC: 1035 AN: 2106

Alfa AF: 0.492 Hom.: 5309

Bravo AF: 0.493

Asia WGS AF: 0.405 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.71
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1403951; hg19: chr1-85940249;