rs233115

Positions:

• chr1-85321294-G-A
• chr1-85321294-G-T

Variant summary

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

The NM_012137.4(DDAH1):​c.*158C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 606,140 control chromosomes in the GnomAD database, including 37,435 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 0.34 (8944 hom., cov: 29)
  • Exomes 𝑓: 0.35 (28491 hom.)
• Consequence: DDAH1 NM_012137.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.*158C>T		3_prime_UTR_variant	6/6	ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.*158C>T		3_prime_UTR_variant	6/6	1	NM_012137.4	ENSP00000284031	P1
BCL10-AS1	ENST00000426125.1	n.67+43556G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51621 AN: 151400 Hom.: 8941 Cov.: 29

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.350 AC: 158933 AN: 454622 Hom.: 28491 Cov.: 4 AF XY: 0.351 AC XY: 84257 AN XY: 239928

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.341 AC: 51641 AN: 151518 Hom.: 8944 Cov.: 29 AF XY: 0.342 AC XY: 25325 AN XY: 74072

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.311

Alfa AF: 0.330 Hom.: 6349

Bravo AF: 0.333

Asia WGS AF: 0.300 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.1
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs233115; hg19: chr1-85786977;