rs28489187

Variant names:

• chr1-85331427-A-G
• rs28489187
• NM_012137.4:c.598-6544T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-85331427-A-G
• chr1-85331427-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000284031.13(DDAH1):​c.598-6544T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.00021 (0 hom., cov: 25)
  • Failed GnomAD Quality Control
• Consequence: DDAH1 ENST00000284031.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000284031.13. 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.598-6544T>C		intron	N/A	NP_036269.1
	DDAH1	NM_001330655.2		c.298-6544T>C		intron	N/A	NP_001317584.1
	DDAH1	NM_001134445.2		c.289-6544T>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.598-6544T>C		intron	N/A	ENSP00000284031.8
	DDAH1	ENST00000426972.8	TSL:1	c.289-6544T>C		intron	N/A	ENSP00000411189.4
	DDAH1	ENST00000633113.1	TSL:2	c.298-6544T>C		intron	N/A	ENSP00000488725.1

Frequencies

GnomAD3 genomes AF: 0.000212 AC: 18 AN: 84904 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000409

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000322

Gnomad SAS AF: 0.000900

Gnomad FIN AF: 0.00143

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000137

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000212 AC: 18 AN: 84976 Hom.: 0 Cov.: 25 AF XY: 0.000312 AC XY: 13 AN XY: 41690

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000407 AC: 1 AN: 24552

American (AMR) AF: 0.000110 AC: 1 AN: 9076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1936

East Asian (EAS) AF: 0.000323 AC: 1 AN: 3098

South Asian (SAS) AF: 0.000900 AC: 2 AN: 2222

European-Finnish (FIN) AF: 0.00143 AC: 8 AN: 5598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 156

European-Non Finnish (NFE) AF: 0.000137 AC: 5 AN: 36610

Other (OTH) AF: 0.00 AC: 0 AN: 1256

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00461 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism

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: rs28489187; hg19: chr1-85797110;