1-85329429-T-C

Variant names:

• chr1-85329429-T-C
• rs233130
• NM_012137.4:c.598-4546A>G

Variant summary

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

The NM_012137.4(DDAH1):​c.598-4546A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,078 control chromosomes in the GnomAD database, including 9,336 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 0.35 (9336 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 10 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012137.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	NM_012137.4	MANE Select	c.598-4546A>G		intron	N/A	NP_036269.1
	DDAH1	NM_001330655.2		c.298-4546A>G		intron	N/A	NP_001317584.1
	DDAH1	NM_001134445.2		c.289-4546A>G		intron	N/A	NP_001127917.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	ENST00000284031.13	TSL:1 MANE Select	c.598-4546A>G		intron	N/A	ENSP00000284031.8
	DDAH1	ENST00000426972.8	TSL:1	c.289-4546A>G		intron	N/A	ENSP00000411189.4
	DDAH1	ENST00000633113.1	TSL:2	c.298-4546A>G		intron	N/A	ENSP00000488725.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52902 AN: 151962 Hom.: 9331 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.348 AC: 52925 AN: 152078 Hom.: 9336 Cov.: 32 AF XY: 0.349 AC XY: 25954 AN XY: 74376

African (AFR) AF: 0.327 AC: 13544 AN: 41454

American (AMR) AF: 0.339 AC: 5178 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1479 AN: 5180

South Asian (SAS) AF: 0.403 AC: 1940 AN: 4818

European-Finnish (FIN) AF: 0.379 AC: 4007 AN: 10578

Middle Eastern (MID) AF: 0.317 AC: 92 AN: 290

European-Non Finnish (NFE) AF: 0.361 AC: 24530 AN: 67970

Other (OTH) AF: 0.316 AC: 668 AN: 2114

Alfa AF: 0.351 Hom.: 25208

Bravo AF: 0.341

Asia WGS AF: 0.301 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.51
PhyloP100		-1.4
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: rs233130; hg19: chr1-85795112;