rs623790

Positions:

• chr1-85517720-A-G

Variant summary

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

The ENST00000426972.8(DDAH1):​c.-122-21439T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,088 control chromosomes in the GnomAD database, including 1,963 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 (1963 hom., cov: 29)
• Consequence: DDAH1 ENST00000426972.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDAH1	NM_001134445.2	c.-122-21439T>C		intron_variant
DDAH1	XM_005270707.3	c.18+60264T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000498304.5	n.268-21439T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22874 AN: 151970 Hom.: 1962 Cov.: 29

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.150 AC: 22889 AN: 152088 Hom.: 1963 Cov.: 29 AF XY: 0.148 AC XY: 11032 AN XY: 74360

Gnomad4 AFR AF: 0.0722

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.125

Alfa AF: 0.163 Hom.: 200

Bravo AF: 0.137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.72
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs623790; hg19: chr1-85983403; COSMIC: COSV71936266;