rs309167

chr2-135911694-C-T

Variant summary

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

The NM_001349.4(DARS1):c.1231-201G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 446,084 control chromosomes in the GnomAD database, including 8,716 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 0.18 (2821 hom., cov: 32)
  • Exomes 𝑓: 0.18 (5895 hom.)
• Consequence: DARS1 NM_001349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

Genes affected

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DARS1	NM_001349.4	c.1231-201G>A		intron_variant		ENST00000264161.9
DARS1	NM_001293312.1	c.931-201G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DARS1	ENST00000264161.9	c.1231-201G>A		intron_variant		1	NM_001349.4	P1
DARS1	ENST00000422708.3	c.292-201G>A		intron_variant		2
DARS1	ENST00000489964.5	n.480-201G>A		intron_variant, non_coding_transcript_variant		2
DARS1	ENST00000491481.1	n.75-201G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27964 AN: 151956 Hom.: 2818 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.181 AC: 53106 AN: 294012 Hom.: 5895 AF XY: 0.186 AC XY: 28735 AN XY: 154588

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.184 AC: 27985 AN: 152072 Hom.: 2821 Cov.: 32 AF XY: 0.187 AC XY: 13896 AN XY: 74332

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.248

Alfa AF: 0.181 Hom.: 404

Bravo AF: 0.189

Asia WGS AF: 0.200 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.2
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: rs309167; hg19: chr2-136669264;