Variant chr11-3038130-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001014437.3(CARS1):c.721G>T(p.Ala241Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00979 in 1,613,960 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 11 hom., cov: 32)

Exomes 𝑓: 0.010 ( 134 hom. )

Consequence

CARS1
NM_001014437.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.330

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0089785755).

BP6

Variant 11-3038130-C-A is Benign according to our data. Variant chr11-3038130-C-A is described in ClinVar as [Benign]. Clinvar id is 775293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00761 (1159/152342) while in subpopulation SAS AF= 0.0232 (112/4830). AF 95% confidence interval is 0.0197. There are 11 homozygotes in gnomad4. There are 567 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARS1	NM_001014437.3 link	c.721G>T	p.Ala241Ser	missense_variant	7/23	ENST00000380525.9	NP_001014437.1	P49589-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARS1	ENST00000380525.9 link	c.721G>T	p.Ala241Ser	missense_variant	7/23	1	NM_001014437.3	ENSP00000369897.4		P49589-3

Frequencies

GnomAD3 genomes

AF:

0.00762

AC:

1160

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00970

AC:

2440

AN:

251484

Hom.:

AF XY:

0.0111

AC XY:

1505

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00650

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0234

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0100

AC:

14638

AN:

1461618

Hom.:

134

Cov.:

AF XY:

0.0106

AC XY:

7716

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00671

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0239

Gnomad4 FIN exome

AF:

0.00404

Gnomad4 NFE exome

AF:

0.00971

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.00761

AC:

1159

AN:

152342

Hom.:

Cov.:

AF XY:

0.00761

AC XY:

567

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.0102

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0232

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00630

Hom.:

Bravo

AF:

0.00710

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00985

AC:

1196

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0105

EpiControl

AF:

0.0143

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 28, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.44

DANN

Benign

0.89

DEOGEN2

Benign

0.065

.;T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.26

MetaRNN

Benign

0.0090

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.33

.;N;N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

0.24

N;N;N;.

REVEL

Benign

0.068

Sift

Benign

0.64

T;T;T;.

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.0030, 0.0050

.;B;B;B

Vest4

0.15

MVP

0.27

MPC

0.23

ClinPred

0.00069

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.054

gMVP

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over