rs553257

Positions:

• chr1-85432647-A-G
• chr1-85432647-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012137.4(DDAH1):​c.303+32096T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,136 control chromosomes in the GnomAD database, including 2,829 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 0.19 (2829 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.303+32096T>C		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+32096T>C		intron_variant		1	NM_012137.4	ENSP00000284031	P1
DDAH1	ENST00000426972.8	c.-7+63519T>C		intron_variant		1		ENSP00000411189
BCL10-AS1	ENST00000426125.1	n.138-15151A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28360 AN: 152018 Hom.: 2825 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0919

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.187 AC: 28387 AN: 152136 Hom.: 2829 Cov.: 32 AF XY: 0.183 AC XY: 13590 AN XY: 74386

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.0925

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.200

Alfa AF: 0.167 Hom.: 2249

Bravo AF: 0.188

Asia WGS AF: 0.127 AC: 444 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.89

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: rs553257; hg19: chr1-85898330;