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GeneBe

11-3017133-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001014437.3(CARS1):c.1890C>A(p.Ile630=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,614,024 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 126 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 122 hom. )

Consequence

CARS1
NM_001014437.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0220
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-3017133-G-T is Benign according to our data. Variant chr11-3017133-G-T is described in ClinVar as [Benign]. Clinvar id is 779130.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.022 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0743 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CARS1NM_001014437.3 linkuse as main transcriptc.1890C>A p.Ile630= synonymous_variant 16/23 ENST00000380525.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CARS1ENST00000380525.9 linkuse as main transcriptc.1890C>A p.Ile630= synonymous_variant 16/231 NM_001014437.3 P3P49589-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0221
AC:
3367
AN:
152138
Hom.:
126
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0767
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00883
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.0143
GnomAD3 exomes
AF:
0.00567
AC:
1424
AN:
251246
Hom.:
50
AF XY:
0.00400
AC XY:
543
AN XY:
135780
show subpopulations
Gnomad AFR exome
AF:
0.0768
Gnomad AMR exome
AF:
0.00347
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000326
Gnomad OTH exome
AF:
0.00245
GnomAD4 exome
AF:
0.00232
AC:
3391
AN:
1461768
Hom.:
122
Cov.:
31
AF XY:
0.00198
AC XY:
1440
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.0792
Gnomad4 AMR exome
AF:
0.00427
Gnomad4 ASJ exome
AF:
0.000191
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000191
Gnomad4 OTH exome
AF:
0.00498
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0221
AC:
3371
AN:
152256
Hom.:
126
Cov.:
32
AF XY:
0.0217
AC XY:
1615
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0765
Gnomad4 AMR
AF:
0.00889
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.0142
Alfa
AF:
0.00130
Hom.:
1
Bravo
AF:
0.0254
Asia WGS
AF:
0.00635
AC:
22
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
4.0
Dann
Benign
0.87
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6

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: rs61737274; hg19: chr11-3038363; API