rs12132677

Variant names:

• chr1-85413930-A-C
• rs12132677
• NM_012137.4:c.303+50813T>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.303+50813T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,256 control chromosomes in the GnomAD database, including 2,297 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 0.16 (2297 hom., cov: 33)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.303+50813T>G		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+50813T>G		intron_variant	Intron 1 of 5	1	NM_012137.4	ENSP00000284031.8
DDAH1	ENST00000426972.8	c.-6-55083T>G		intron_variant	Intron 2 of 6	1		ENSP00000411189.4
BCL10-AS1	ENST00000426125.1	n.138-33868A>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24006 AN: 152138 Hom.: 2296 Cov.: 33

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.158 AC: 23998 AN: 152256 Hom.: 2297 Cov.: 33 AF XY: 0.158 AC XY: 11774 AN XY: 74444

African (AFR) AF: 0.0485 AC: 2017 AN: 41566

American (AMR) AF: 0.221 AC: 3383 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 654 AN: 3472

East Asian (EAS) AF: 0.141 AC: 731 AN: 5186

South Asian (SAS) AF: 0.116 AC: 561 AN: 4828

European-Finnish (FIN) AF: 0.220 AC: 2335 AN: 10598

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13693 AN: 68008

Other (OTH) AF: 0.179 AC: 379 AN: 2116

Alfa AF: 0.169 Hom.: 299

Bravo AF: 0.155

Asia WGS AF: 0.102 AC: 355 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		1.9
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: rs12132677; hg19: chr1-85879613;