dbSNP rs7481584: CARS1:c.2069-900C>T (chr11-3007859-G-A) – 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.2069-900C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,174 control chromosomes in the GnomAD database, including 7,059 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 0.28 ( 7055 hom., cov: 32)

Exomes 𝑓: 0.33 ( 4 hom. )

Consequence

CARS1
NM_001014437.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.453

Publications

38 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 (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARS1	NM_001014437.3 link	c.2069-900C>T		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.2069-900C>T		intron_variant	Intron 18 of 22	1	NM_001014437.3	ENSP00000369897.4		P49589-3

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42217

AN:

151974

Hom.:

7042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.481

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.360

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.329

AC:

AN:

Hom.:

Cov.:

AF XY:

0.343

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.297

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.278

AC:

42246

AN:

152092

Hom.:

7055

Cov.:

AF XY:

0.281

AC XY:

20907

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.137

AC:

5698

AN:

41500

American (AMR)

AF:

0.444

AC:

6787

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.360

AC:

1250

AN:

3468

East Asian (EAS)

AF:

0.629

AC:

3248

AN:

5160

South Asian (SAS)

AF:

0.403

AC:

1941

AN:

4818

European-Finnish (FIN)

AF:

0.222

AC:

2345

AN:

10574

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.291

AC:

19786

AN:

67972

Other (OTH)

AF:

0.311

AC:

659

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1471

2942

4413

5884

7355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.292

Hom.:

11838

Bravo

AF:

0.288

Asia WGS

AF:

0.499

AC:

1734

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

1.4

(source)

DANN

Benign

0.29

PhyloP100

-0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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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rs7481584

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