1-85458237-G-A

Position:

• chr1-85458237-G-A

Variant summary

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

The NM_012137.4(DDAH1):​c.303+6506C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,874 control chromosomes in the GnomAD database, including 10,100 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 0.36 (10100 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.303+6506C>T		intron_variant		ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.303+6506C>T		intron_variant		1	NM_012137.4	ENSP00000284031	P1
DDAH1	ENST00000426972.8	c.-7+37929C>T		intron_variant		1		ENSP00000411189

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55194 AN: 151756 Hom.: 10083 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.364 AC: 55247 AN: 151874 Hom.: 10100 Cov.: 32 AF XY: 0.363 AC XY: 26974 AN XY: 74228

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.371

Alfa AF: 0.388 Hom.: 8024

Bravo AF: 0.367

Asia WGS AF: 0.321 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.38

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: rs877041; hg19: chr1-85923920;