1-85454076-A-C

Position:

• chr1-85454076-A-C

Variant summary

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

The NM_012137.4(DDAH1):​c.303+10667T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,740 control chromosomes in the GnomAD database, including 5,086 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 (5086 hom., cov: 31)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352

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 = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.303+10667T>G		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+10667T>G		intron_variant		1	NM_012137.4	ENSP00000284031	P1
DDAH1	ENST00000426972.8	c.-7+42090T>G		intron_variant		1		ENSP00000411189

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38375 AN: 151626 Hom.: 5078 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.253 AC: 38396 AN: 151740 Hom.: 5086 Cov.: 31 AF XY: 0.253 AC XY: 18767 AN XY: 74118

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0815

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.269

Alfa AF: 0.249 Hom.: 1768

Bravo AF: 0.251

Asia WGS AF: 0.193 AC: 671 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	4.0
DANN	Benign	0.58

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: rs13373844; hg19: chr1-85919759;