Variant rs6738266 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001349.4(DARS1):c.-134G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,524,210 control chromosomes in the GnomAD database, including 431 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 0.029 ( 77 hom., cov: 33)

Exomes 𝑓: 0.019 ( 354 hom. )

Consequence

DARS1
NM_001349.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.254

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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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
DARS1	NM_001349.4 linkuse as main transcript	c.-134G>A	5_prime_UTR_variant	1/16	ENST00000264161.9	NP_001340.2
DARS1-AS1	NR_110199.1 linkuse as main transcript	n.341+86C>T	intron_variant, non_coding_transcript_variant
DARS1	NM_001293312.1 linkuse as main transcript	c.-376G>A	5_prime_UTR_variant	1/15		NP_001280241.1
DARS1-AS1	NR_110200.1 linkuse as main transcript	n.341+86C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DARS1	ENST00000264161.9 linkuse as main transcript	c.-134G>A		5_prime_UTR_variant	1/16	1	NM_001349.4	ENSP00000264161	P1	P14868-1
DARS1-AS1	ENST00000692958.1 linkuse as main transcript	n.393+86C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4348

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0385

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0279

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.0594

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.0223

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0279

AC:

3921

AN:

140644

Hom.:

AF XY:

0.0265

AC XY:

2030

AN XY:

76510

show subpopulations

Gnomad AFR exome

AF:

0.0433

Gnomad AMR exome

AF:

0.0338

Gnomad ASJ exome

AF:

0.0390

Gnomad EAS exome

AF:

0.0549

Gnomad SAS exome

AF:

0.0163

Gnomad FIN exome

AF:

0.0245

Gnomad NFE exome

AF:

0.0222

Gnomad OTH exome

AF:

0.0291

GnomAD4 exome

AF:

0.0192

AC:

26322

AN:

1371924

Hom.:

354

Cov.:

AF XY:

0.0195

AC XY:

13109

AN XY:

673836

show subpopulations

Gnomad4 AFR exome

AF:

0.0404

Gnomad4 AMR exome

AF:

0.0300

Gnomad4 ASJ exome

AF:

0.0360

Gnomad4 EAS exome

AF:

0.0546

Gnomad4 SAS exome

AF:

0.0159

Gnomad4 FIN exome

AF:

0.0227

Gnomad4 NFE exome

AF:

0.0164

Gnomad4 OTH exome

AF:

0.0241

GnomAD4 genome

AF:

0.0286

AC:

4357

AN:

152286

Hom.:

Cov.:

AF XY:

0.0286

AC XY:

2127

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0384

Gnomad4 AMR

AF:

0.0281

Gnomad4 ASJ

AF:

0.0409

Gnomad4 EAS

AF:

0.0597

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0223

Gnomad4 NFE

AF:

0.0219

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0254

Hom.:

Bravo

AF:

0.0294

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.6

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over