1-85449719-C-T

Position:

• chr1-85449719-C-T

Variant summary

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

The NM_012137.4(DDAH1):​c.303+15024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,850 control chromosomes in the GnomAD database, including 10,821 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 0.34 (10821 hom., cov: 31)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.303+15024G>A		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+15024G>A		intron_variant		1	NM_012137.4	ENSP00000284031.8
DDAH1	ENST00000426972.8	c.-7+46447G>A		intron_variant		1		ENSP00000411189.4

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52311 AN: 151730 Hom.: 10818 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.345 AC: 52315 AN: 151850 Hom.: 10821 Cov.: 31 AF XY: 0.346 AC XY: 25679 AN XY: 74160

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.396

Alfa AF: 0.429 Hom.: 19723

Bravo AF: 0.339

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.039
DANN	Benign	0.36

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: rs11161618; hg19: chr1-85915402;