chr1-85474422-T-G

Variant names:

• chr1-85474422-T-G
• rs1403955
• ENST00000426972.8:c.-7+21744A>C

Variant summary

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

The ENST00000426972.8(DDAH1):​c.-7+21744A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,734 control chromosomes in the GnomAD database, including 11,960 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 0.40 (11960 hom., cov: 31)
• Consequence: DDAH1 ENST00000426972.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• Publications: 11 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000426972.8. 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_001134445.2		c.-7+21744A>C		intron	N/A	NP_001127917.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDAH1	ENST00000426972.8	TSL:1	c.-7+21744A>C		intron	N/A	ENSP00000411189.4

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60162 AN: 151612 Hom.: 11950 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.397 AC: 60208 AN: 151734 Hom.: 11960 Cov.: 31 AF XY: 0.399 AC XY: 29555 AN XY: 74136

African (AFR) AF: 0.374 AC: 15468 AN: 41388

American (AMR) AF: 0.400 AC: 6103 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1322 AN: 3466

East Asian (EAS) AF: 0.324 AC: 1665 AN: 5140

South Asian (SAS) AF: 0.506 AC: 2419 AN: 4776

European-Finnish (FIN) AF: 0.420 AC: 4400 AN: 10486

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27534 AN: 67912

Other (OTH) AF: 0.380 AC: 802 AN: 2112

Alfa AF: 0.398 Hom.: 20978

Bravo AF: 0.390

Asia WGS AF: 0.351 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.79
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1403955; hg19: chr1-85940105;