NM_012137.4:c.*1384A>G

Variant names:

• chr1-85320068-T-C
• rs233112
• NM_012137.4:c.*1384A>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.*1384A>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 0.366 in 152,076 control chromosomes in the GnomAD database, including 10,288 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 0.37 (10287 hom., cov: 32)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: DDAH1 NM_012137.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 31 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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDAH1	NM_012137.4	c.*1384A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000284031.13	NP_036269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDAH1	ENST00000284031.13	c.*1384A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_012137.4	ENSP00000284031.8

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55598 AN: 151950 Hom.: 10280 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.366 AC: 55639 AN: 152068 Hom.: 10287 Cov.: 32 AF XY: 0.366 AC XY: 27230 AN XY: 74338

African (AFR) AF: 0.332 AC: 13779 AN: 41464

American (AMR) AF: 0.355 AC: 5421 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1334 AN: 3470

East Asian (EAS) AF: 0.409 AC: 2113 AN: 5170

South Asian (SAS) AF: 0.424 AC: 2041 AN: 4812

European-Finnish (FIN) AF: 0.383 AC: 4051 AN: 10582

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25693 AN: 67970

Other (OTH) AF: 0.348 AC: 734 AN: 2112

Alfa AF: 0.372 Hom.: 40782

Bravo AF: 0.361

Asia WGS AF: 0.382 AC: 1326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.9
DANN	Benign	0.63
PhyloP100		0.0010
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: rs233112; hg19: chr1-85785751;