rs2071101

Variant summary

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

The NM_001014437.3(CARS1):​c.1031+89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 908,756 control chromosomes in the GnomAD database, including 4,630 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 0.025 ( 533 hom., cov: 32)
Exomes 𝑓: 0.033 ( 4097 hom. )

Consequence

CARS1
NM_001014437.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36
Variant links:
Genes affected
CARS1 (HGNC:1493): (cysteinyl-tRNA synthetase 1) This gene encodes a class 1 aminoacyl-tRNA synthetase, cysteinyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. This gene is one of several located near the imprinted gene domain on chromosome 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CARS1NM_001014437.3 linkuse as main transcriptc.1031+89G>A intron_variant ENST00000380525.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CARS1ENST00000380525.9 linkuse as main transcriptc.1031+89G>A intron_variant 1 NM_001014437.3 P3P49589-3

Frequencies

GnomAD3 genomes
AF:
0.0249
AC:
3783
AN:
152164
Hom.:
533
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00417
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0623
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.430
Gnomad SAS
AF:
0.0573
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00154
Gnomad OTH
AF:
0.0244
GnomAD4 exome
AF:
0.0330
AC:
24941
AN:
756474
Hom.:
4097
Cov.:
10
AF XY:
0.0324
AC XY:
12909
AN XY:
398478
show subpopulations
Gnomad4 AFR exome
AF:
0.00349
Gnomad4 AMR exome
AF:
0.0924
Gnomad4 ASJ exome
AF:
0.00291
Gnomad4 EAS exome
AF:
0.445
Gnomad4 SAS exome
AF:
0.0458
Gnomad4 FIN exome
AF:
0.000332
Gnomad4 NFE exome
AF:
0.00163
Gnomad4 OTH exome
AF:
0.0341
GnomAD4 genome
AF:
0.0249
AC:
3785
AN:
152282
Hom.:
533
Cov.:
32
AF XY:
0.0280
AC XY:
2084
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.00416
Gnomad4 AMR
AF:
0.0623
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.431
Gnomad4 SAS
AF:
0.0565
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00154
Gnomad4 OTH
AF:
0.0255
Alfa
AF:
0.00821
Hom.:
8
Bravo
AF:
0.0304
Asia WGS
AF:
0.203
AC:
703
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
9.2
DANN
Benign
0.86

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

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

Other links and lift over

dbSNP: rs2071101; hg19: chr11-3050137; COSMIC: COSV53450338; COSMIC: COSV53450338; API