rs17590006

Variant names:

• chr1-85323587-A-G
• rs17590006
• NM_012137.4:c.741+1153T>C

Variant summary

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

The NM_012137.4(DDAH1):​c.741+1153T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,098 control chromosomes in the GnomAD database, including 2,900 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 0.18 (2900 hom., cov: 31)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 2 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]

BCL10-AS1 (HGNC:55868): (BCL10 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.741+1153T>C		intron_variant	Intron 5 of 5	ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.741+1153T>C		intron_variant	Intron 5 of 5	1	NM_012137.4	ENSP00000284031.8

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26940 AN: 151978 Hom.: 2893 Cov.: 31

Gnomad AFR AF: 0.0581

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0952

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.177 AC: 26952 AN: 152098 Hom.: 2900 Cov.: 31 AF XY: 0.179 AC XY: 13325 AN XY: 74332

African (AFR) AF: 0.0580 AC: 2410 AN: 41528

American (AMR) AF: 0.248 AC: 3790 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3470

East Asian (EAS) AF: 0.0953 AC: 492 AN: 5164

South Asian (SAS) AF: 0.191 AC: 919 AN: 4810

European-Finnish (FIN) AF: 0.225 AC: 2381 AN: 10566

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15551 AN: 67966

Other (OTH) AF: 0.207 AC: 435 AN: 2106

Alfa AF: 0.220 Hom.: 6630

Bravo AF: 0.174

Asia WGS AF: 0.161 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.70
PhyloP100		-0.022
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: rs17590006; hg19: chr1-85789270;