rs877041

Variant names:

• chr1-85458237-G-A
• rs877041
• NM_012137.4:c.303+6506C>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+6506C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,874 control chromosomes in the GnomAD database, including 10,100 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 0.36 (10100 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• 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 (AMR) allele frequency at 95% confidence interval = 0.41 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	NM_012137.4	MANE Select	c.303+6506C>T		intron	N/A	NP_036269.1	B2R644
	DDAH1	NM_001134445.2		c.-7+37929C>T		intron	N/A	NP_001127917.1	O94760-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	ENST00000284031.13	TSL:1 MANE Select	c.303+6506C>T		intron	N/A	ENSP00000284031.8	O94760-1
	DDAH1	ENST00000426972.8	TSL:1	c.-7+37929C>T		intron	N/A	ENSP00000411189.4	O94760-2
	DDAH1	ENST00000866624.1		c.303+6506C>T		intron	N/A	ENSP00000536683.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55194 AN: 151756 Hom.: 10083 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.364 AC: 55247 AN: 151874 Hom.: 10100 Cov.: 32 AF XY: 0.363 AC XY: 26974 AN XY: 74228

African (AFR) AF: 0.312 AC: 12908 AN: 41400

American (AMR) AF: 0.418 AC: 6383 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1106 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1578 AN: 5160

South Asian (SAS) AF: 0.250 AC: 1206 AN: 4826

European-Finnish (FIN) AF: 0.386 AC: 4051 AN: 10502

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26800 AN: 67938

Other (OTH) AF: 0.371 AC: 784 AN: 2112

Alfa AF: 0.384 Hom.: 14830

Bravo AF: 0.367

Asia WGS AF: 0.321 AC: 1118 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	0.46
DANN	Benign	0.38
PhyloP100		-0.36
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: rs877041; hg19: chr1-85923920;