dbSNP rs2071101: CARS1:c.1031+89G>A (chr11-3028907-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

8 publications found

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]

CARS1 links:

CARS1-AS1 (HGNC:40125): (CARS1 antisense RNA 1)

CARS1-AS1 links:

Genome browser will be placed here

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=-0.77).

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 rank	MANE	Protein	UniProt
CARS1	NM_001014437.3 link	c.1031+89G>A		intron_variant	Intron 9 of 22	ENST00000380525.9	NP_001014437.1	P49589-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARS1	ENST00000380525.9 link	c.1031+89G>A		intron_variant	Intron 9 of 22	1	NM_001014437.3	ENSP00000369897.4		P49589-3

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3783

AN:

152164

Hom.:

533

Cov.:

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.:

AF XY:

0.0324

AC XY:

12909

AN XY:

398478

show subpopulations

African (AFR)

AF:

0.00349

AC:

AN:

19504

American (AMR)

AF:

0.0924

AC:

3484

AN:

37712

Ashkenazi Jewish (ASJ)

AF:

0.00291

AC:

AN:

19584

East Asian (EAS)

AF:

0.445

AC:

16174

AN:

36342

South Asian (SAS)

AF:

0.0458

AC:

3081

AN:

67296

European-Finnish (FIN)

AF:

0.000332

AC:

AN:

51250

Middle Eastern (MID)

AF:

0.00501

AC:

AN:

2794

European-Non Finnish (NFE)

AF:

0.00163

AC:

792

AN:

485230

Other (OTH)

AF:

0.0341

AC:

1254

AN:

36762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

870

1740

2609

3479

4349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.0249

AC:

3785

AN:

152282

Hom.:

533

Cov.:

AF XY:

0.0280

AC XY:

2084

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00416

AC:

173

AN:

41562

American (AMR)

AF:

0.0623

AC:

954

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.431

AC:

2217

AN:

5144

South Asian (SAS)

AF:

0.0565

AC:

273

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00154

AC:

105

AN:

68028

Other (OTH)

AF:

0.0255

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

137

275

412

550

687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.00821

Hom.:

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

(source)

DANN

Benign

0.86

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over