rs587843

chr1-85471958-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000426972.8(DDAH1):c.-7+24208G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,024 control chromosomes in the GnomAD database, including 31,387 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 0.63 (31387 hom., cov: 32)
• Consequence: DDAH1 ENST00000426972.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDAH1	NM_001134445.2	c.-7+24208G>C		intron_variant
DDAH1	XM_005270707.3	c.18+106026G>C		intron_variant
DDAH1	XM_011541158.2	c.-87+24208G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDAH1	ENST00000426972.8	c.-7+24208G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96292 AN: 151904 Hom.: 31366 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.634 AC: 96340 AN: 152024 Hom.: 31387 Cov.: 32 AF XY: 0.637 AC XY: 47337 AN XY: 74328

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.651

Alfa AF: 0.669 Hom.: 4324

Bravo AF: 0.626

Asia WGS AF: 0.598 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.9
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587843; hg19: chr1-85937641; COSMIC: COSV72271966; COSMIC: COSV72271966;