rs2284798

Variant names:

• chr1-85348895-A-G
• rs2284798
• NM_012137.4:c.597+1520T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012137.4(DDAH1):​c.597+1520T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 152,284 control chromosomes in the GnomAD database, including 297 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 0.053 (297 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 2 publications found

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]

BCL10-AS1 (HGNC:55868): (BCL10 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.597+1520T>C		intron_variant	Intron 4 of 5	ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.597+1520T>C		intron_variant	Intron 4 of 5	1	NM_012137.4	ENSP00000284031.8

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8144 AN: 152166 Hom.: 297 Cov.: 32

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.0478

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

GnomAD4 genome AF: 0.0535 AC: 8143 AN: 152284 Hom.: 297 Cov.: 32 AF XY: 0.0564 AC XY: 4200 AN XY: 74464

African (AFR) AF: 0.0499 AC: 2074 AN: 41552

American (AMR) AF: 0.0314 AC: 480 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3468

East Asian (EAS) AF: 0.160 AC: 828 AN: 5182

South Asian (SAS) AF: 0.184 AC: 885 AN: 4818

European-Finnish (FIN) AF: 0.0484 AC: 514 AN: 10622

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0447 AC: 3044 AN: 68026

Other (OTH) AF: 0.0477 AC: 101 AN: 2116

Alfa AF: 0.0440 Hom.: 21

Bravo AF: 0.0500

Asia WGS AF: 0.138 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2284798; hg19: chr1-85814578;