rs480414

Variant names:

• chr1-85461780-G-A
• rs480414
• NM_012137.4:c.303+2963C>T

Variant summary

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

The NM_012137.4(DDAH1):​c.303+2963C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,040 control chromosomes in the GnomAD database, including 7,639 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 0.31 (7639 hom., cov: 33)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444
• Publications: 19 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.303+2963C>T		intron_variant	Intron 1 of 5	ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.303+2963C>T		intron_variant	Intron 1 of 5	1	NM_012137.4	ENSP00000284031.8
DDAH1	ENST00000426972.8	c.-7+34386C>T		intron_variant	Intron 2 of 6	1		ENSP00000411189.4

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47755 AN: 151922 Hom.: 7630 Cov.: 33

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.314 AC: 47786 AN: 152040 Hom.: 7639 Cov.: 33 AF XY: 0.313 AC XY: 23276 AN XY: 74320

African (AFR) AF: 0.378 AC: 15682 AN: 41450

American (AMR) AF: 0.243 AC: 3714 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1164 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1390 AN: 5168

South Asian (SAS) AF: 0.421 AC: 2028 AN: 4814

European-Finnish (FIN) AF: 0.266 AC: 2806 AN: 10562

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 20013 AN: 67976

Other (OTH) AF: 0.297 AC: 627 AN: 2108

Alfa AF: 0.300 Hom.: 20853

Bravo AF: 0.312

Asia WGS AF: 0.331 AC: 1154 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	7.4
DANN	Benign	0.78
PhyloP100		0.44
Mutation Taster		=100/0	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: rs480414; hg19: chr1-85927463;