NM_012137.4:c.303+8869T>C

Variant names:

• chr1-85455874-A-G
• rs3738111
• NM_012137.4:c.303+8869T>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.303+8869T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,276 control chromosomes in the GnomAD database, including 1,084 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 0.11 (1084 hom., cov: 33)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 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.303+8869T>C		intron	N/A	NP_036269.1
	DDAH1	NM_001134445.2		c.-7+40292T>C		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.303+8869T>C		intron	N/A	ENSP00000284031.8
	DDAH1	ENST00000426972.8	TSL:1	c.-7+40292T>C		intron	N/A	ENSP00000411189.4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16934 AN: 152158 Hom.: 1083 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0935

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.0537

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.111 AC: 16941 AN: 152276 Hom.: 1084 Cov.: 33 AF XY: 0.108 AC XY: 8077 AN XY: 74450

African (AFR) AF: 0.175 AC: 7259 AN: 41532

American (AMR) AF: 0.0934 AC: 1429 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 591 AN: 3472

East Asian (EAS) AF: 0.0824 AC: 428 AN: 5192

South Asian (SAS) AF: 0.0533 AC: 257 AN: 4822

European-Finnish (FIN) AF: 0.0662 AC: 703 AN: 10612

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0866 AC: 5890 AN: 68028

Other (OTH) AF: 0.117 AC: 247 AN: 2108

Alfa AF: 0.0806 Hom.: 200

Bravo AF: 0.117

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.5
DANN	Benign	0.75
PhyloP100		0.097
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: rs3738111; hg19: chr1-85921557;