1-85458781-T-C

Variant names:

• chr1-85458781-T-C
• rs12568675
• NM_012137.4:c.303+5962A>G

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+5962A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 152,188 control chromosomes in the GnomAD database, including 877 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 0.092 (877 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.303+5962A>G		intron_variant	Intron 1 of 5	ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.303+5962A>G		intron_variant	Intron 1 of 5	1	NM_012137.4	ENSP00000284031.8
DDAH1	ENST00000426972.8	c.-7+37385A>G		intron_variant	Intron 2 of 6	1		ENSP00000411189.4

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14056 AN: 152070 Hom.: 873 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0890

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

GnomAD4 genome AF: 0.0924 AC: 14063 AN: 152188 Hom.: 877 Cov.: 32 AF XY: 0.0922 AC XY: 6858 AN XY: 74392

African (AFR) AF: 0.0216 AC: 899 AN: 41546

American (AMR) AF: 0.129 AC: 1977 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0525 AC: 182 AN: 3468

East Asian (EAS) AF: 0.226 AC: 1171 AN: 5176

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4818

European-Finnish (FIN) AF: 0.116 AC: 1231 AN: 10568

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8080 AN: 68002

Other (OTH) AF: 0.0876 AC: 185 AN: 2112

Alfa AF: 0.106 Hom.: 2937

Bravo AF: 0.0943

Asia WGS AF: 0.125 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.66
PhyloP100		-0.69
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: rs12568675; hg19: chr1-85924464; COSMIC: COSV52302300;