chr1-85411415-C-T

Variant names:

• chr1-85411415-C-T
• rs1554597
• NM_012137.4:c.304-52568G>A

Variant summary

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

The NM_012137.4(DDAH1):​c.304-52568G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,004 control chromosomes in the GnomAD database, including 32,797 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 0.66 (32797 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• 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]

BCL10-AS1 (HGNC:55868): (BCL10 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.304-52568G>A		intron_variant	Intron 1 of 5	ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.304-52568G>A		intron_variant	Intron 1 of 5	1	NM_012137.4	ENSP00000284031.8
DDAH1	ENST00000426972.8	c.-6-52568G>A		intron_variant	Intron 2 of 6	1		ENSP00000411189.4
BCL10-AS1	ENST00000426125.1	n.137+34580C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99537 AN: 151886 Hom.: 32756 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.655 AC: 99634 AN: 152004 Hom.: 32797 Cov.: 32 AF XY: 0.654 AC XY: 48569 AN XY: 74294

African (AFR) AF: 0.699 AC: 29001 AN: 41478

American (AMR) AF: 0.657 AC: 10045 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2300 AN: 3468

East Asian (EAS) AF: 0.714 AC: 3668 AN: 5138

South Asian (SAS) AF: 0.595 AC: 2871 AN: 4828

European-Finnish (FIN) AF: 0.619 AC: 6528 AN: 10550

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43013 AN: 67944

Other (OTH) AF: 0.676 AC: 1429 AN: 2114

Alfa AF: 0.649 Hom.: 5405

Bravo AF: 0.663

Asia WGS AF: 0.701 AC: 2441 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	0.032
DANN	Benign	0.26
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1554597; hg19: chr1-85877098;