1-85321435-G-C

Position:

• chr1-85321435-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012137.4(DDAH1):​c.*17C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,556,668 control chromosomes in the GnomAD database, including 102,191 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 0.29 (7250 hom., cov: 31)
  • Exomes 𝑓: 0.37 (94941 hom.)
• Consequence: DDAH1 NM_012137.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDAH1	NM_012137.4	c.*17C>G		3_prime_UTR_variant	6/6	ENST00000284031.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDAH1	ENST00000284031.13	c.*17C>G		3_prime_UTR_variant	6/6	1	NM_012137.4	P1
BCL10-AS1	ENST00000426125.1	n.67+43697G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43899 AN: 151848 Hom.: 7251 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.278

GnomAD3 exomes AF: 0.343 AC: 85847 AN: 249954 Hom.: 15441 AF XY: 0.352 AC XY: 47506 AN XY: 135148

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.300

Gnomad SAS exome AF: 0.408

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.357

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.366 AC: 513649 AN: 1404704 Hom.: 94941 Cov.: 24 AF XY: 0.366 AC XY: 257044 AN XY: 701904

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.408

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.289 AC: 43893 AN: 151964 Hom.: 7250 Cov.: 31 AF XY: 0.292 AC XY: 21697 AN XY: 74268

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.277

Alfa AF: 0.216 Hom.: 649

Bravo AF: 0.273

Asia WGS AF: 0.293 AC: 1017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.15
DANN	Benign	0.54

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: rs3087894; hg19: chr1-85787118; COSMIC: COSV52303953; COSMIC: COSV52303953;