dbSNP rs12363575: CARS1:c.2069-1915T>C (chr11-3008874-A-G) – 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.2069-1915T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,064 control chromosomes in the GnomAD database, including 2,616 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 0.18 ( 2613 hom., cov: 31)

Exomes 𝑓: 0.27 ( 3 hom. )

Consequence

CARS1
NM_001014437.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.264

Publications

9 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 Gene-Disease associations (from GenCC):

microcephaly, developmental delay, and brittle hair syndrome
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics

CARS1 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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARS1	NM_001014437.3 link	c.2069-1915T>C		intron_variant	Intron 18 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.2069-1915T>C		intron_variant	Intron 18 of 22	1	NM_001014437.3	ENSP00000369897.4		P49589-3

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27169

AN:

151876

Hom.:

2614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.0996

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.193

GnomAD4 exome

AF:

0.271

AC:

AN:

Hom.:

Cov.:

AF XY:

0.226

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.293

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.579

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.179

AC:

27165

AN:

151994

Hom.:

2613

Cov.:

AF XY:

0.177

AC XY:

13168

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.114

AC:

4748

AN:

41472

American (AMR)

AF:

0.150

AC:

2283

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

754

AN:

3470

East Asian (EAS)

AF:

0.142

AC:

732

AN:

5146

South Asian (SAS)

AF:

0.100

AC:

484

AN:

4826

European-Finnish (FIN)

AF:

0.240

AC:

2535

AN:

10568

Middle Eastern (MID)

AF:

0.226

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.220

AC:

14917

AN:

67944

Other (OTH)

AF:

0.190

AC:

400

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1117

2234

3352

4469

5586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.202

Hom.:

5527

Bravo

AF:

0.171

Asia WGS

AF:

0.119

AC:

414

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.2

(source)

DANN

Benign

0.52

PhyloP100

-0.26

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