dbSNP rs2278683: DARS1:c.-34+10T>G (chr2-135985920-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000456565.5(DARS1):c.-34+10T>G variant causes a intron 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
ENST00000456565.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00400

Publications

9 publications found

Variant links:

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]

DARS1 links:

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

DARS1-AS1 links:

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new If you want to explore the variant's impact on the transcript ENST00000456565.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000456565.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
DARS1-AS1	NR_110199.1	n.341+404A>C	intron	N/A
DARS1-AS1	NR_110200.1	n.341+404A>C	intron	N/A
DARS1	NM_001293312.1	c.-694T>G	upstream_gene	N/A	NP_001280241.1	P14868-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DARS1	ENST00000456565.5	TSL:3	c.-34+10T>G	intron	N/A	ENSP00000397616.1	C9J7S3
DARS1-AS1	ENST00000444406.1	TSL:2	n.226A>C	non_coding_transcript_exon	Exon 2 of 2
DARS1-AS1	ENST00000764020.1		n.383A>C	non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28834

AN:

152064

Hom.:

3340

Cov.:

show subpopulations

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.:

AF XY:

0.222

AC XY:

2970

AN XY:

13382

show subpopulations

African (AFR)

AF:

0.280

AC:

276

AN:

986

American (AMR)

AF:

0.353

AC:

812

AN:

2300

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

149

AN:

520

East Asian (EAS)

AF:

0.198

AC:

225

AN:

1136

South Asian (SAS)

AF:

0.341

AC:

1564

AN:

4586

European-Finnish (FIN)

AF:

0.160

AC:

102

AN:

636

Middle Eastern (MID)

AF:

0.279

AC:

AN:

European-Non Finnish (NFE)

AF:

0.126

AC:

1603

AN:

12694

Other (OTH)

AF:

0.173

AC:

205

AN:

1186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.543

Heterozygous variant carriers

174

348

523

697

871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.190

AC:

28854

AN:

152182

Hom.:

3344

Cov.:

AF XY:

0.197

AC XY:

14640

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.248

AC:

10284

AN:

41492

American (AMR)

AF:

0.306

AC:

4686

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

948

AN:

3472

East Asian (EAS)

AF:

0.191

AC:

990

AN:

5178

South Asian (SAS)

AF:

0.353

AC:

1706

AN:

4830

European-Finnish (FIN)

AF:

0.145

AC:

1539

AN:

10592

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8072

AN:

68002

Other (OTH)

AF:

0.217

AC:

459

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1177

2355

3532

4710

5887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.152

Hom.:

4802

Bravo

AF:

0.203

Asia WGS

AF:

0.286

AC:

994

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.2

(source)

DANN

Benign

0.56

PhyloP100

0.0040

PromoterAI

-0.013

Neutral

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over