1-85321651-C-T

Variant names:

• chr1-85321651-C-T
• rs1498374
• NM_012137.4:c.742-83G>A

Variant summary

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

The NM_012137.4(DDAH1):​c.742-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,056,364 control chromosomes in the GnomAD database, including 18,544 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 0.15 (2128 hom., cov: 32)
  • Exomes 𝑓: 0.19 (16416 hom.)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698
• Publications: 9 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.742-83G>A		intron_variant	Intron 5 of 5	ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.742-83G>A		intron_variant	Intron 5 of 5	1	NM_012137.4	ENSP00000284031.8

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22963 AN: 152082 Hom.: 2127 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.187 AC: 169052 AN: 904164 Hom.: 16416 AF XY: 0.184 AC XY: 86484 AN XY: 469944

African (AFR) AF: 0.0364 AC: 808 AN: 22192

American (AMR) AF: 0.211 AC: 8809 AN: 41744

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 3818 AN: 21380

East Asian (EAS) AF: 0.104 AC: 3833 AN: 36828

South Asian (SAS) AF: 0.118 AC: 8446 AN: 71724

European-Finnish (FIN) AF: 0.226 AC: 11528 AN: 50928

Middle Eastern (MID) AF: 0.145 AC: 667 AN: 4610

European-Non Finnish (NFE) AF: 0.202 AC: 123728 AN: 613070

Other (OTH) AF: 0.178 AC: 7415 AN: 41688

GnomAD4 genome AF: 0.151 AC: 22955 AN: 152200 Hom.: 2128 Cov.: 32 AF XY: 0.151 AC XY: 11262 AN XY: 74434

African (AFR) AF: 0.0407 AC: 1691 AN: 41550

American (AMR) AF: 0.213 AC: 3252 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3468

East Asian (EAS) AF: 0.140 AC: 726 AN: 5168

South Asian (SAS) AF: 0.110 AC: 531 AN: 4828

European-Finnish (FIN) AF: 0.217 AC: 2295 AN: 10590

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13237 AN: 67984

Other (OTH) AF: 0.167 AC: 352 AN: 2112

Alfa AF: 0.177 Hom.: 7492

Bravo AF: 0.147

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.17
DANN	Benign	0.23
PhyloP100		-0.70
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: rs1498374; hg19: chr1-85787334; COSMIC: COSV52303253;