chr1-85423913-G-A

Variant names:

• chr1-85423913-G-A
• rs7521189
• NM_012137.4:c.303+40830C>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.303+40830C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,844 control chromosomes in the GnomAD database, including 16,819 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 0.46 (16819 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 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+40830C>T		intron	N/A	NP_036269.1	B2R644
	DDAH1	NM_001134445.2		c.-6-65066C>T		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+40830C>T		intron	N/A	ENSP00000284031.8	O94760-1
	DDAH1	ENST00000426972.8	TSL:1	c.-6-65066C>T		intron	N/A	ENSP00000411189.4	O94760-2
	DDAH1	ENST00000866624.1		c.303+40830C>T		intron	N/A	ENSP00000536683.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70526 AN: 151726 Hom.: 16795 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.465 AC: 70597 AN: 151844 Hom.: 16819 Cov.: 32 AF XY: 0.462 AC XY: 34245 AN XY: 74200

African (AFR) AF: 0.529 AC: 21910 AN: 41430

American (AMR) AF: 0.469 AC: 7144 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1776 AN: 3464

East Asian (EAS) AF: 0.187 AC: 968 AN: 5166

South Asian (SAS) AF: 0.353 AC: 1697 AN: 4812

European-Finnish (FIN) AF: 0.439 AC: 4620 AN: 10522

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 30986 AN: 67894

Other (OTH) AF: 0.489 AC: 1032 AN: 2110

Alfa AF: 0.462 Hom.: 53834

Bravo AF: 0.470

Asia WGS AF: 0.344 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.72
PhyloP100		-1.0
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: rs7521189; hg19: chr1-85889596; COSMIC: COSV107312412;