chr1-85459425-T-G

Position:

• chr1-85459425-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012137.4(DDAH1):​c.303+5318A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,144 control chromosomes in the GnomAD database, including 5,187 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 0.25 (5187 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDAH1	NM_012137.4	c.303+5318A>C		intron_variant		ENST00000284031.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDAH1	ENST00000284031.13	c.303+5318A>C		intron_variant		1	NM_012137.4	P1
DDAH1	ENST00000426972.8	c.-7+36741A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37603 AN: 152026 Hom.: 5186 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.247 AC: 37601 AN: 152144 Hom.: 5187 Cov.: 32 AF XY: 0.251 AC XY: 18666 AN XY: 74364

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.254

Alfa AF: 0.247 Hom.: 740

Bravo AF: 0.237

Asia WGS AF: 0.261 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs974874; hg19: chr1-85925108;