rs2278683

chr2-135985920-A-C

Variant summary

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

The NR_110199.1(DARS1-AS1):n.341+404A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 176,312 control chromosomes in the GnomAD database, including 4,055 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 0.19 (3344 hom., cov: 32)
  • Exomes 𝑓: 0.21 (711 hom.)
• Consequence: DARS1-AS1 NR_110199.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

Genes affected

DARS1-AS1 (HGNC:40170): (DARS1 antisense RNA 1)

DARS1 (HGNC:2678): (aspartyl-tRNA synthetase 1) This gene encodes a member of a multienzyme complex that functions in mediating the attachment of amino acids to their cognate tRNAs. The encoded protein ligates L-aspartate to tRNA(Asp). Mutations in this gene have been found in patients showing hypomyelination with brainstem and spinal cord involvement and leg spasticity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DARS1-AS1	NR_110199.1	n.341+404A>C		intron_variant, non_coding_transcript_variant
DARS1-AS1	NR_110200.1	n.341+404A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DARS1-AS1	ENST00000692958.1	n.393+404A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28834 AN: 152064 Hom.: 3340 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.206 AC: 4960 AN: 24130 Hom.: 711 Cov.: 0 AF XY: 0.222 AC XY: 2970 AN XY: 13382

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.190 AC: 28854 AN: 152182 Hom.: 3344 Cov.: 32 AF XY: 0.197 AC XY: 14640 AN XY: 74408

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.217

Alfa AF: 0.142 Hom.: 2734

Bravo AF: 0.203

Asia WGS AF: 0.286 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.2
Dann	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2278683; hg19: chr2-136743490;