rs1523993

Positions:

• chr1-85433445-C-T

Variant summary

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

The NM_012137.4(DDAH1):​c.303+31298G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,000 control chromosomes in the GnomAD database, including 5,536 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 0.27 (5536 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.303+31298G>A		intron_variant		ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.303+31298G>A		intron_variant		1	NM_012137.4	ENSP00000284031	P1
DDAH1	ENST00000426972.8	c.-7+62721G>A		intron_variant		1		ENSP00000411189
BCL10-AS1	ENST00000426125.1	n.138-14353C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40480 AN: 151882 Hom.: 5528 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0951

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.266 AC: 40504 AN: 152000 Hom.: 5536 Cov.: 32 AF XY: 0.267 AC XY: 19833 AN XY: 74316

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.0953

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.273

Alfa AF: 0.274 Hom.: 12160

Bravo AF: 0.268

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.75

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: rs1523993; hg19: chr1-85899128;