1-85361769-G-A

Variant names:

• chr1-85361769-G-A
• rs2474123
• NM_012137.4:c.304-2922C>T

Variant summary

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

The NM_012137.4(DDAH1):​c.304-2922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,936 control chromosomes in the GnomAD database, including 12,903 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 0.41 (12903 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 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.304-2922C>T		intron	N/A	NP_036269.1
	DDAH1	NM_001330655.2		c.4-2922C>T		intron	N/A	NP_001317584.1
	DDAH1	NM_001134445.2		c.-6-2922C>T		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.304-2922C>T		intron	N/A	ENSP00000284031.8
	DDAH1	ENST00000426972.8	TSL:1	c.-6-2922C>T		intron	N/A	ENSP00000411189.4
	DDAH1	ENST00000633113.1	TSL:2	c.4-2922C>T		intron	N/A	ENSP00000488725.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62017 AN: 151818 Hom.: 12903 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.408 AC: 62052 AN: 151936 Hom.: 12903 Cov.: 32 AF XY: 0.413 AC XY: 30670 AN XY: 74260

African (AFR) AF: 0.344 AC: 14264 AN: 41438

American (AMR) AF: 0.383 AC: 5839 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1477 AN: 3460

East Asian (EAS) AF: 0.568 AC: 2928 AN: 5152

South Asian (SAS) AF: 0.606 AC: 2918 AN: 4816

European-Finnish (FIN) AF: 0.432 AC: 4553 AN: 10536

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28710 AN: 67970

Other (OTH) AF: 0.387 AC: 817 AN: 2110

Alfa AF: 0.264 Hom.: 764

Bravo AF: 0.399

Asia WGS AF: 0.518 AC: 1795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.50
PhyloP100		0.48
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: rs2474123; hg19: chr1-85827452;