rs2474123

Positions:

• chr1-85361769-G-A
• chr1-85361769-G-C

Variant summary

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

The NM_012137.4(DDAH1):​c.304-2922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,936 control chromosomes in the GnomAD database, including 12,903 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 0.41 (12903 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDAH1	NM_012137.4	c.304-2922C>T		intron_variant		ENST00000284031.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDAH1	ENST00000284031.13	c.304-2922C>T		intron_variant		1	NM_012137.4	P1
BCL10-AS1	ENST00000426125.1	n.68-14997G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62017 AN: 151818 Hom.: 12903 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.408 AC: 62052 AN: 151936 Hom.: 12903 Cov.: 32 AF XY: 0.413 AC XY: 30670 AN XY: 74260

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.387

Alfa AF: 0.264 Hom.: 764

Bravo AF: 0.399

Asia WGS AF: 0.518 AC: 1795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs2474123; hg19: chr1-85827452;