1-85427706-T-C

Variant names:

• chr1-85427706-T-C
• rs17388437
• NM_012137.4:c.303+37037A>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+37037A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 152,284 control chromosomes in the GnomAD database, including 179 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 0.038 (179 hom., cov: 33)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 4 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=-0.47).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 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+37037A>G		intron	N/A	NP_036269.1	B2R644
	DDAH1	NM_001134445.2		c.-7+68460A>G		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+37037A>G		intron	N/A	ENSP00000284031.8	O94760-1
	DDAH1	ENST00000426972.8	TSL:1	c.-7+68460A>G		intron	N/A	ENSP00000411189.4	O94760-2
	DDAH1	ENST00000866624.1		c.303+37037A>G		intron	N/A	ENSP00000536683.1

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5790 AN: 152166 Hom.: 179 Cov.: 33

Gnomad AFR AF: 0.00888

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0540

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0380 AC: 5793 AN: 152284 Hom.: 179 Cov.: 33 AF XY: 0.0382 AC XY: 2845 AN XY: 74452

African (AFR) AF: 0.00883 AC: 367 AN: 41570

American (AMR) AF: 0.0201 AC: 308 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 330 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.129 AC: 624 AN: 4820

European-Finnish (FIN) AF: 0.0291 AC: 309 AN: 10610

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0540 AC: 3674 AN: 68012

Other (OTH) AF: 0.0288 AC: 61 AN: 2116

Alfa AF: 0.0556 Hom.: 254

Bravo AF: 0.0338

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		0.058
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: rs17388437; hg19: chr1-85893389;