chr1-85433745-T-C

Variant names:

• chr1-85433745-T-C
• rs669173
• NM_012137.4:c.303+30998A>G

Variant summary

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

The NM_012137.4(DDAH1):​c.303+30998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,032 control chromosomes in the GnomAD database, including 13,767 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 0.42 (13767 hom., cov: 32)
• Consequence: DDAH1 NM_012137.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.303+30998A>G		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.303+30998A>G		intron_variant	Intron 1 of 5	1	NM_012137.4	ENSP00000284031.8
DDAH1	ENST00000426972.8	c.-7+62421A>G		intron_variant	Intron 2 of 6	1		ENSP00000411189.4
BCL10-AS1	ENST00000426125.1	n.138-14053T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64253 AN: 151914 Hom.: 13753 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.423 AC: 64310 AN: 152032 Hom.: 13767 Cov.: 32 AF XY: 0.425 AC XY: 31548 AN XY: 74284

African (AFR) AF: 0.454 AC: 18840 AN: 41480

American (AMR) AF: 0.412 AC: 6295 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3468

East Asian (EAS) AF: 0.264 AC: 1366 AN: 5172

South Asian (SAS) AF: 0.490 AC: 2363 AN: 4818

European-Finnish (FIN) AF: 0.422 AC: 4450 AN: 10540

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28280 AN: 67964

Other (OTH) AF: 0.423 AC: 892 AN: 2110

Alfa AF: 0.423 Hom.: 7171

Bravo AF: 0.421

Asia WGS AF: 0.399 AC: 1386 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.46
DANN	Benign	0.51
PhyloP100		-1.0
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: rs669173; hg19: chr1-85899428;