ENST00000426972.8:c.-7+24208G>C

Variant names:

• chr1-85471958-C-G
• rs587843
• ENST00000426972.8:c.-7+24208G>C

Variant summary

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

The ENST00000426972.8(DDAH1):​c.-7+24208G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,024 control chromosomes in the GnomAD database, including 31,387 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 0.63 (31387 hom., cov: 32)
• Consequence: DDAH1 ENST00000426972.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 4 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]

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 (AMR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_001134445.2	c.-7+24208G>C		intron_variant	Intron 2 of 6		NP_001127917.1
DDAH1	XM_005270707.3	c.18+106026G>C		intron_variant	Intron 1 of 5		XP_005270764.1
DDAH1	XM_011541158.2	c.-87+24208G>C		intron_variant	Intron 1 of 6		XP_011539460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000426972.8	c.-7+24208G>C		intron_variant	Intron 2 of 6	1		ENSP00000411189.4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96292 AN: 151904 Hom.: 31366 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.634 AC: 96340 AN: 152024 Hom.: 31387 Cov.: 32 AF XY: 0.637 AC XY: 47337 AN XY: 74328

African (AFR) AF: 0.455 AC: 18843 AN: 41430

American (AMR) AF: 0.733 AC: 11201 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2272 AN: 3472

East Asian (EAS) AF: 0.621 AC: 3200 AN: 5156

South Asian (SAS) AF: 0.590 AC: 2844 AN: 4818

European-Finnish (FIN) AF: 0.744 AC: 7876 AN: 10584

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47949 AN: 67972

Other (OTH) AF: 0.651 AC: 1373 AN: 2110

Alfa AF: 0.669 Hom.: 4324

Bravo AF: 0.626

Asia WGS AF: 0.598 AC: 2078 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	2.9
DANN	Benign	0.70
PhyloP100		0.30
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: rs587843; hg19: chr1-85937641; COSMIC: COSV72271966; COSMIC: COSV72271966;