1-85555486-A-G

Variant names:

• chr1-85555486-A-G
• rs11161637
• ENST00000426972.8:c.-123+22498T>C

Variant summary

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

The ENST00000426972.8(DDAH1):​c.-123+22498T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,058 control chromosomes in the GnomAD database, including 10,548 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 0.36 (10548 hom., cov: 32)
• Consequence: DDAH1 ENST00000426972.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• Publications: 6 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]

ENSG00000282057 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_001134445.2	c.-123+22498T>C		intron_variant	Intron 1 of 6		NP_001127917.1
DDAH1	XM_005270707.3	c.18+22498T>C		intron_variant	Intron 1 of 5		XP_005270764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000426972.8	c.-123+22498T>C		intron_variant	Intron 1 of 6	1		ENSP00000411189.4
ENSG00000282057	ENST00000467530.5	n.167+22498T>C		intron_variant	Intron 1 of 2	2
ENSG00000282057	ENST00000467666.2	n.275+20346T>C		intron_variant	Intron 2 of 3	3
ENSG00000282057	ENST00000498304.5	n.267+22498T>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55315 AN: 151940 Hom.: 10545 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.364 AC: 55332 AN: 152058 Hom.: 10548 Cov.: 32 AF XY: 0.361 AC XY: 26861 AN XY: 74328

African (AFR) AF: 0.262 AC: 10891 AN: 41504

American (AMR) AF: 0.351 AC: 5368 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3468

East Asian (EAS) AF: 0.282 AC: 1459 AN: 5176

South Asian (SAS) AF: 0.208 AC: 1004 AN: 4818

European-Finnish (FIN) AF: 0.466 AC: 4910 AN: 10534

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28833 AN: 67962

Other (OTH) AF: 0.372 AC: 785 AN: 2110

Alfa AF: 0.400 Hom.: 48084

Bravo AF: 0.353

Asia WGS AF: 0.251 AC: 871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.16
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11161637; hg19: chr1-86021169;