NM_012137.4:c.598-67C>T

Variant names:

• chr1-85324950-G-A
• rs1498373
• NM_012137.4:c.598-67C>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.598-67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,577,218 control chromosomes in the GnomAD database, including 101,950 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 0.29 (7223 hom., cov: 31)
  • Exomes 𝑓: 0.36 (94727 hom.)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571
• Publications: 21 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=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.598-67C>T		intron_variant	Intron 4 of 5	ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.598-67C>T		intron_variant	Intron 4 of 5	1	NM_012137.4	ENSP00000284031.8

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43780 AN: 151876 Hom.: 7225 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.361 AC: 513905 AN: 1425226 Hom.: 94727 AF XY: 0.362 AC XY: 255427 AN XY: 706428

African (AFR) AF: 0.108 AC: 3562 AN: 32896

American (AMR) AF: 0.342 AC: 14856 AN: 43438

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 8115 AN: 25170

East Asian (EAS) AF: 0.256 AC: 10018 AN: 39184

South Asian (SAS) AF: 0.407 AC: 33665 AN: 82770

European-Finnish (FIN) AF: 0.397 AC: 18860 AN: 47562

Middle Eastern (MID) AF: 0.289 AC: 1582 AN: 5474

European-Non Finnish (NFE) AF: 0.370 AC: 403329 AN: 1089742

Other (OTH) AF: 0.338 AC: 19918 AN: 58990

GnomAD4 genome AF: 0.288 AC: 43771 AN: 151992 Hom.: 7223 Cov.: 31 AF XY: 0.291 AC XY: 21614 AN XY: 74280

African (AFR) AF: 0.119 AC: 4925 AN: 41500

American (AMR) AF: 0.317 AC: 4830 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1159 AN: 3460

East Asian (EAS) AF: 0.286 AC: 1473 AN: 5156

South Asian (SAS) AF: 0.402 AC: 1935 AN: 4812

European-Finnish (FIN) AF: 0.379 AC: 3991 AN: 10542

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24467 AN: 67956

Other (OTH) AF: 0.275 AC: 580 AN: 2110

Alfa AF: 0.332 Hom.: 4869

Bravo AF: 0.273

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		-0.57
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: rs1498373; hg19: chr1-85790633; COSMIC: COSV52302015;