NM_012137.4:c.304-37446G>C

Variant names:

• chr1-85396293-C-G
• rs2177461
• NM_012137.4:c.304-37446G>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.304-37446G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,000 control chromosomes in the GnomAD database, including 32,840 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 0.66 (32840 hom., cov: 31)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 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.304-37446G>C		intron	N/A	NP_036269.1
	DDAH1	NM_001330655.2		c.3+8088G>C		intron	N/A	NP_001317584.1
	DDAH1	NM_001134445.2		c.-6-37446G>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.304-37446G>C		intron	N/A	ENSP00000284031.8
	DDAH1	ENST00000426972.8	TSL:1	c.-6-37446G>C		intron	N/A	ENSP00000411189.4
	DDAH1	ENST00000633113.1	TSL:2	c.3+8088G>C		intron	N/A	ENSP00000488725.1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99595 AN: 151882 Hom.: 32799 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.656 AC: 99693 AN: 152000 Hom.: 32840 Cov.: 31 AF XY: 0.655 AC XY: 48625 AN XY: 74290

African (AFR) AF: 0.698 AC: 28942 AN: 41442

American (AMR) AF: 0.658 AC: 10045 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2304 AN: 3472

East Asian (EAS) AF: 0.711 AC: 3675 AN: 5166

South Asian (SAS) AF: 0.596 AC: 2874 AN: 4826

European-Finnish (FIN) AF: 0.620 AC: 6551 AN: 10562

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43093 AN: 67954

Other (OTH) AF: 0.675 AC: 1424 AN: 2110

Alfa AF: 0.648 Hom.: 3968

Bravo AF: 0.664

Asia WGS AF: 0.702 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.91
DANN	Benign	0.59
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2177461; hg19: chr1-85861976;