1-85462196-A-G

Variant names:

• chr1-85462196-A-G
• rs1241321
• NM_012137.4:c.303+2547T>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.303+2547T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,000 control chromosomes in the GnomAD database, including 7,859 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 0.32 (7859 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 19 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012137.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	NM_012137.4	MANE Select	c.303+2547T>C		intron	N/A	NP_036269.1
	DDAH1	NM_001134445.2		c.-7+33970T>C		intron	N/A	NP_001127917.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	ENST00000284031.13	TSL:1 MANE Select	c.303+2547T>C		intron	N/A	ENSP00000284031.8
	DDAH1	ENST00000426972.8	TSL:1	c.-7+33970T>C		intron	N/A	ENSP00000411189.4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48726 AN: 151882 Hom.: 7843 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.321 AC: 48768 AN: 152000 Hom.: 7859 Cov.: 32 AF XY: 0.321 AC XY: 23842 AN XY: 74296

African (AFR) AF: 0.314 AC: 13005 AN: 41438

American (AMR) AF: 0.286 AC: 4369 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2051 AN: 5158

South Asian (SAS) AF: 0.406 AC: 1956 AN: 4816

European-Finnish (FIN) AF: 0.323 AC: 3411 AN: 10564

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22232 AN: 67962

Other (OTH) AF: 0.282 AC: 594 AN: 2110

Alfa AF: 0.320 Hom.: 21944

Bravo AF: 0.318

Asia WGS AF: 0.368 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.51
PhyloP100		-0.27
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: rs1241321; hg19: chr1-85927879;