1-85438655-C-T

Variant names:

• chr1-85438655-C-T
• rs539714
• NM_012137.4:c.303+26088G>A

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+26088G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,158 control chromosomes in the GnomAD database, including 50,952 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 0.82 (50952 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.87 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	NM_012137.4	MANE Select	c.303+26088G>A		intron	N/A	NP_036269.1	B2R644
	DDAH1	NM_001134445.2		c.-7+57511G>A		intron	N/A	NP_001127917.1	O94760-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	ENST00000284031.13	TSL:1 MANE Select	c.303+26088G>A		intron	N/A	ENSP00000284031.8	O94760-1
	DDAH1	ENST00000426972.8	TSL:1	c.-7+57511G>A		intron	N/A	ENSP00000411189.4	O94760-2
	DDAH1	ENST00000866624.1		c.303+26088G>A		intron	N/A	ENSP00000536683.1

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124197 AN: 152038 Hom.: 50912 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.859

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

GnomAD4 genome AF: 0.817 AC: 124295 AN: 152158 Hom.: 50952 Cov.: 32 AF XY: 0.816 AC XY: 60680 AN XY: 74372

African (AFR) AF: 0.757 AC: 31399 AN: 41496

American (AMR) AF: 0.882 AC: 13490 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2997 AN: 3472

East Asian (EAS) AF: 0.851 AC: 4385 AN: 5152

South Asian (SAS) AF: 0.715 AC: 3448 AN: 4822

European-Finnish (FIN) AF: 0.840 AC: 8891 AN: 10588

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56847 AN: 68014

Other (OTH) AF: 0.857 AC: 1812 AN: 2114

Alfa AF: 0.831 Hom.: 195615

Bravo AF: 0.822

Asia WGS AF: 0.803 AC: 2795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.73
PhyloP100		-0.86
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: rs539714; hg19: chr1-85904338;