rs2290000

Positions:

• chr11-3052608-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001014437.3(CARS1):​c.26-4607T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 152,274 control chromosomes in the GnomAD database, including 65,468 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 0.93 (65468 hom., cov: 32)
• Consequence: CARS1 NM_001014437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARS1	NM_001014437.3	c.26-4607T>A		intron_variant		ENST00000380525.9	NP_001014437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARS1	ENST00000380525.9	c.26-4607T>A		intron_variant		1	NM_001014437.3	ENSP00000369897.4

Frequencies

GnomAD3 genomes AF: 0.927 AC: 141032 AN: 152156 Hom.: 65422 Cov.: 32

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.925

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.927 AC: 141136 AN: 152274 Hom.: 65468 Cov.: 32 AF XY: 0.925 AC XY: 68825 AN XY: 74440

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.944

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.918

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.926

Alfa AF: 0.926 Hom.: 8092

Bravo AF: 0.931

Asia WGS AF: 0.908 AC: 3156 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	1.6
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2290000; hg19: chr11-3073838;